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University of Arizona
1.
Huynh, Julie.
ESCRT-Dependent Cell Death in a Caenorhabditis elegans Model of the Lysosomal Storage Disorder Mucolipidosis Type IV
.
Degree: 2015, University of Arizona
URL: http://hdl.handle.net/10150/595811 
► Mutations in MCOLN1, which encodes the cation channel protein TRPML1, result in the neurodegenerative lysosomal storage disorder Mucolipidosis type IV. Mucolipidosis type IV patients show…
(more)
▼ Mutations in MCOLN1, which encodes the cation channel protein TRPML1, result in the neurodegenerative lysosomal storage disorder Mucolipidosis type IV. Mucolipidosis type IV patients show lysosomal dysfunction in many tissues and neuronal cell death. The orthologue of TRPML1 in Caenorhabditis elegans is CUP-5; loss of CUP-5 results in lysosomal dysfunction in many tissues and death of developing intestinal cells that results in embryonic lethality. We previously showed that a null mutation in the ATP-Binding Cassette transporter MRP-4 rescues the lysosomal defect and embryonic lethality of cup-5(null) worms. Here we show that reducing levels of the Endosomal Sorting Complex Required for Transport (ESCRT)-associated proteins DID-2, PHI-33, and ALX-1/EGO-2, which mediate the final de-ubiquitination step of integral membrane proteins being sequestered into late endosomes, also almost fully suppress cup-5(null) mutant lysosomal defects and embryonic lethality. Indeed, we show that MRP-4 protein is hypo-ubiquitinated in the absence of CUP-5 and that reducing levels of ESCRT-associated proteins suppresses this hypo-ubiquitination. Thus, increased ESCRT-associated de-ubiquitinating activity mediates the lysosomal defects and corresponding cell death phenotypes in the absence of CUP-5.
Advisors/Committee Members: Fares, Hanna (advisor), Fares, Hanna (committeemember), Tax, Frans (committeemember), Yao, Guang (committeemember).
Subjects/Keywords: ESCRT;
Lysosome;
Mucolipidosis type IV;
TRPML-1;
Molecular & Cellular Biology;
CUP-5
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APA (6th Edition):
Huynh, J. (2015). ESCRT-Dependent Cell Death in a Caenorhabditis elegans Model of the Lysosomal Storage Disorder Mucolipidosis Type IV
. (Masters Thesis). University of Arizona. Retrieved from http://hdl.handle.net/10150/595811
Chicago Manual of Style (16th Edition):
Huynh, Julie. “ESCRT-Dependent Cell Death in a Caenorhabditis elegans Model of the Lysosomal Storage Disorder Mucolipidosis Type IV
.” 2015. Masters Thesis, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/595811.
MLA Handbook (7th Edition):
Huynh, Julie. “ESCRT-Dependent Cell Death in a Caenorhabditis elegans Model of the Lysosomal Storage Disorder Mucolipidosis Type IV
.” 2015. Web. 25 Jan 2021.
Vancouver:
Huynh J. ESCRT-Dependent Cell Death in a Caenorhabditis elegans Model of the Lysosomal Storage Disorder Mucolipidosis Type IV
. [Internet] [Masters thesis]. University of Arizona; 2015. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/595811.
Council of Science Editors:
Huynh J. ESCRT-Dependent Cell Death in a Caenorhabditis elegans Model of the Lysosomal Storage Disorder Mucolipidosis Type IV
. [Masters Thesis]. University of Arizona; 2015. Available from: http://hdl.handle.net/10150/595811
University of Arizona
2.
Gee, Kevin.
Forward Genetic Screen to Identify Proteins Involved in Lysosome Formation
.
Degree: 2017, University of Arizona
URL: http://hdl.handle.net/10150/624124
► Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. Lysosomes are the terminal compartments in the endocytic pathway, though they…
(more)
▼ Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. Lysosomes are the terminal compartments in the endocytic pathway, though they display highly dynamic behaviors, fusing with each other and with late endosomes in the endocytic pathway, and with the plasma membrane during regulated exocytosis and for wound repair. After fusing with late endosomes, lysosomes are reformed from the resulting hybrid organelles through a process that involves budding of a nascent lysosome, extension of the nascent lysosome from the hybrid organelle, while remaining connected by a membrane bridge, and scission of the membrane bridge to release the newly formed lysosome. The newly formed lysosomes undergo cycles of homotypic fusion and fission reactions to form mature lysosomes. In this study, we used a forward genetic screen in Caenorhabditis elegans to identify six regulators of lysosome biology. We show that these proteins function in different steps of lysosome biology, regulating lysosome formation, lysosome fusion, and lysosome degradation.
Advisors/Committee Members: Fares, Hanna F (advisor), Fares, Hanna F. (committeemember), Yao, Guang (committeemember), Buchan, John R. (committeemember).
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APA (6th Edition):
Gee, K. (2017). Forward Genetic Screen to Identify Proteins Involved in Lysosome Formation
. (Masters Thesis). University of Arizona. Retrieved from http://hdl.handle.net/10150/624124
Chicago Manual of Style (16th Edition):
Gee, Kevin. “Forward Genetic Screen to Identify Proteins Involved in Lysosome Formation
.” 2017. Masters Thesis, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/624124.
MLA Handbook (7th Edition):
Gee, Kevin. “Forward Genetic Screen to Identify Proteins Involved in Lysosome Formation
.” 2017. Web. 25 Jan 2021.
Vancouver:
Gee K. Forward Genetic Screen to Identify Proteins Involved in Lysosome Formation
. [Internet] [Masters thesis]. University of Arizona; 2017. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/624124.
Council of Science Editors:
Gee K. Forward Genetic Screen to Identify Proteins Involved in Lysosome Formation
. [Masters Thesis]. University of Arizona; 2017. Available from: http://hdl.handle.net/10150/624124
University of Arizona
3.
Liu, Ian.
Identifying Regulators of Lysosome Reformation: Inhibitor Screen in Mammalian Cell Culture
.
Degree: 2016, University of Arizona
URL: http://hdl.handle.net/10150/613352
► Lysosomes are membrane-bound organelles that have diverse functions in eukaryotic cells. Malfunctions in lysosomes result in a range of diseases known as Lysosomal Storage Disorders.…
(more)
▼ Lysosomes are membrane-bound organelles that have diverse functions in eukaryotic cells. Malfunctions in lysosomes result in a range of diseases known as Lysosomal Storage Disorders. After fusing with late endosomes to form hybrid organelles, lysosomes bud off and are reformed in a poorly characterized process known as lysosome formation or reformation. Only one mammalian regulator of lysosome formation has been identified, the non-selective cation channel TRPML1. In the highly similar process of Autophagic Lysosome Reformation (ALR), three known regulators have also been identified, the vesicle-coating protein clathrin and two phosphatidylinositol kinases that catalyze the formation of the membrane phospholipid PI(4,5)P₂. Here, we use an inhibitor screen coupled with a live imaging assay to identify the actin microfilament as a novel regulator of lysosome formation.
Advisors/Committee Members: Fares, Hanna (advisor), Laney, Jeff (committeemember), Buchan, Ross (committeemember).
Subjects/Keywords: Lysosomal formation;
Lysosome;
Lysosome biogenesis;
Molecular & Cellular Biology;
Endocytosis
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APA (6th Edition):
Liu, I. (2016). Identifying Regulators of Lysosome Reformation: Inhibitor Screen in Mammalian Cell Culture
. (Masters Thesis). University of Arizona. Retrieved from http://hdl.handle.net/10150/613352
Chicago Manual of Style (16th Edition):
Liu, Ian. “Identifying Regulators of Lysosome Reformation: Inhibitor Screen in Mammalian Cell Culture
.” 2016. Masters Thesis, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/613352.
MLA Handbook (7th Edition):
Liu, Ian. “Identifying Regulators of Lysosome Reformation: Inhibitor Screen in Mammalian Cell Culture
.” 2016. Web. 25 Jan 2021.
Vancouver:
Liu I. Identifying Regulators of Lysosome Reformation: Inhibitor Screen in Mammalian Cell Culture
. [Internet] [Masters thesis]. University of Arizona; 2016. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/613352.
Council of Science Editors:
Liu I. Identifying Regulators of Lysosome Reformation: Inhibitor Screen in Mammalian Cell Culture
. [Masters Thesis]. University of Arizona; 2016. Available from: http://hdl.handle.net/10150/613352
University of Arizona
4.
Jain, Saumya.
The Analysis of mRNP Granule Composition and Structure in Saccharomyces cerevisiae
.
Degree: 2015, University of Arizona
URL: http://hdl.handle.net/10150/556224
► A recurring theme in biology is the aggregation of mRNA-protein complexes (mRNPs) into higher order assemblies. Often these complexes play important roles in the regulation…
(more)
▼ A recurring theme in biology is the aggregation of mRNA-protein complexes (mRNPs) into higher order assemblies. Often these complexes play important roles in the regulation of gene expression, but the function of the conserved cytoplasmic mRNP assemblies - P bodies and stress granules, is not known. It is believed that the misregulation of granule assembly is related to disorders like Amyotrophic Lateral Sclerosis and Frontotemporal Lobe Degeneration. Determining the complete composition of these granules may hold the key to understanding the function and mechanism of assembly of these granules. This work describes multiple approaches taken to identify new protein and mRNA components of P bodies and stress granules. New members of the P body and stress granule proteome reveal a role for these granules in diverse cellular processes including signal transduction, transcription and metabolism. Additionally, a new stress granule resident complex - the CCT complex, was also identified as a novel regulator of granule disassembly. This work also describes the first purification scheme for stress granules and presents a new system for in vitro study of stress granules. Together, the findings shed new light on the composition, function, structure and regulation of P bodies and stress granules in yeast.
Advisors/Committee Members: Fares, Hanna (advisor), Parker, Roy (advisor), Fares, Hanna (committeemember), Parker, Roy (committeemember), Weinert, Ted (committeemember), Capaldi, Andrew (committeemember), Zarnescu, Daniela (committeemember).
Subjects/Keywords: P Bodies;
Stress Granules;
Molecular & Cellular Biology;
mRNA binding proteins
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APA ·
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APA (6th Edition):
Jain, S. (2015). The Analysis of mRNP Granule Composition and Structure in Saccharomyces cerevisiae
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/556224
Chicago Manual of Style (16th Edition):
Jain, Saumya. “The Analysis of mRNP Granule Composition and Structure in Saccharomyces cerevisiae
.” 2015. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/556224.
MLA Handbook (7th Edition):
Jain, Saumya. “The Analysis of mRNP Granule Composition and Structure in Saccharomyces cerevisiae
.” 2015. Web. 25 Jan 2021.
Vancouver:
Jain S. The Analysis of mRNP Granule Composition and Structure in Saccharomyces cerevisiae
. [Internet] [Doctoral dissertation]. University of Arizona; 2015. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/556224.
Council of Science Editors:
Jain S. The Analysis of mRNP Granule Composition and Structure in Saccharomyces cerevisiae
. [Doctoral Dissertation]. University of Arizona; 2015. Available from: http://hdl.handle.net/10150/556224
University of Arizona
5.
Swisher, Kylie.
Assembly of mRNP Complexes During Stress and Nonsense-Mediated mRNA Decay Quality Control in Saccharomyces cerevisiae
.
Degree: 2011, University of Arizona
URL: http://hdl.handle.net/10150/204068
► In eukaryotes, mRNA is in constant flux between an actively translating state and translationally repressed states. Specifically, mRNA degradation and repression factors compete with translation…
(more)
▼ In eukaryotes, mRNA is in constant flux between an actively translating state and translationally repressed states. Specifically, mRNA degradation and repression factors compete with translation factors to direct mRNAs out of translation for storage or decay. This process often leads to formation of cytoplasmic aggregates. P-bodies are granules that contain mRNA and degradation factors, suggesting they are sites of mRNA decay or storage. Stress granules form in response to stress conditions and contain mRNAs and translation factors.P-bodies and stress granules consist of mRNPs of different compositions, believed to mature and transition between the states. It is proposed that mRNAs transition between the two granules. In the work described below, we use Saccharomyces cerevisiae to demonstrate that a decay factor, Dhh1 is capable of existing in both P-body and stress granule mRNPs. This suggests that a decay factor can be part of two different mRNP complexes. Additionally, we identify two novel components of the stress granule mRNPs, Pbp4 and Lsm12, and determine that they are not essential for stress granule formation. Lastly, we show that the stress granule mRNP factor, Pab1, is not absolutely required for stress granule formation.An important aspect of cytoplasmic mRNA regulation is mRNA quality control. One example of this is nonsense-mediated mRNA decay (NMD), whereby aberrant mRNAs containing premature termination codons are targeted for decay, and can be localized to P-bodies. Upf1-3 and the mRNA decapping complex, Dcp2/Dcp1 are essential for NMD, which requires Upf1 interaction with stalled ribosomal/mRNA complexes to target aberrant mRNA for decapping and degradation. How Dcp2/Dcp1 is recruited to aberrant mRNA is poorly understood.Here, we show by yeast two-hybrid assays that an interaction between Dcp2 and Upf1 is mediated by the decapping stimulator Edc3. Interestingly, Edc3 and Upf2 share overlapping binding sites on the Upf1 N-terminal domain. The decapping stimulator, Pat1, also interacts on the Upf1 N-terminus, but Edc3 and Pat1 are not essential for NMD. Surprisingly, the Upf1-Edc3 interaction does not promote or negatively regulate NMD. Thus, the Upf1-Edc3 and Upf1-Pat1 interactions likely regulate a subset of mRNA transcripts, or are essential for proper NMD under different environmental conditions.
Advisors/Committee Members: Parker, Roy (advisor), Dieckmann, Carol (committeemember), Fares, Hanna (committeemember), Tax, Frans (committeemember).
Subjects/Keywords: mRNA decay;
mRNA regulation;
NMD;
Saccharomyces cerevisiae;
stress granules
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Manager
APA (6th Edition):
Swisher, K. (2011). Assembly of mRNP Complexes During Stress and Nonsense-Mediated mRNA Decay Quality Control in Saccharomyces cerevisiae
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/204068
Chicago Manual of Style (16th Edition):
Swisher, Kylie. “Assembly of mRNP Complexes During Stress and Nonsense-Mediated mRNA Decay Quality Control in Saccharomyces cerevisiae
.” 2011. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/204068.
MLA Handbook (7th Edition):
Swisher, Kylie. “Assembly of mRNP Complexes During Stress and Nonsense-Mediated mRNA Decay Quality Control in Saccharomyces cerevisiae
.” 2011. Web. 25 Jan 2021.
Vancouver:
Swisher K. Assembly of mRNP Complexes During Stress and Nonsense-Mediated mRNA Decay Quality Control in Saccharomyces cerevisiae
. [Internet] [Doctoral dissertation]. University of Arizona; 2011. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/204068.
Council of Science Editors:
Swisher K. Assembly of mRNP Complexes During Stress and Nonsense-Mediated mRNA Decay Quality Control in Saccharomyces cerevisiae
. [Doctoral Dissertation]. University of Arizona; 2011. Available from: http://hdl.handle.net/10150/204068
University of Arizona
6.
Wierzba, Michael.
A Family of Four LRR-RLKs Modulate Development and Defense Signaling in Arabidopsis thaliana through Interaction with the Co-receptor BAK1
.
Degree: 2014, University of Arizona
URL: http://hdl.handle.net/10150/312668
► Receptor-like kinases (RLKs) are encoded for by one of the largest gene families in Arabidopsis and represent the predominant form of cell surface receptors in…
(more)
▼ Receptor-like kinases (RLKs) are encoded for by one of the largest gene families in Arabidopsis and represent the predominant form of cell surface receptors in plants. RLKs mediate signal transduction in diverse processes including steroid-mediated growth pathways, pathogen-triggered innate immune responses. Here I present characterization of mutant phenotypes, expression patterns, and genetic interactions for the BAK1 INTERACTING RECEPTOR (BIR) family of Leucine-rich Repeat-RLKs, three members of which have had no previous characterization. Furthermore, I show that cell death, aerial growth, and lateral root development defects in bir1-1 are suppressed by mutations of the LRR-RLK co-receptor BRI1-ASSOCIATED KINASE 1 (BAK1); I identify a novel primary root growth phenotype in bir1-1 mutants, as well as a lateral root development phenotype for bir3 mutants; and primary root growth and aerial defects in bir3.bir4;bak1 triple mutants. Using an allelic series of bak1 mutations I show that bir phenotypes are dependent upon particular functions of BAK1, and propose that the BIR family exhibits a novel function, previously undescribed for LRR-RLKs, as regulators of co-receptor/ligand-binding receptor complex specificity.
Advisors/Committee Members: Tax, Frans E (advisor), Fares, Hanna (committeemember), Schroeder, Joyce (committeemember), Weinert, Ted (committeemember).
Subjects/Keywords: Receptor-like kinase;
Molecular & Cellular Biology;
Plant development
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APA (6th Edition):
Wierzba, M. (2014). A Family of Four LRR-RLKs Modulate Development and Defense Signaling in Arabidopsis thaliana through Interaction with the Co-receptor BAK1
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/312668
Chicago Manual of Style (16th Edition):
Wierzba, Michael. “A Family of Four LRR-RLKs Modulate Development and Defense Signaling in Arabidopsis thaliana through Interaction with the Co-receptor BAK1
.” 2014. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/312668.
MLA Handbook (7th Edition):
Wierzba, Michael. “A Family of Four LRR-RLKs Modulate Development and Defense Signaling in Arabidopsis thaliana through Interaction with the Co-receptor BAK1
.” 2014. Web. 25 Jan 2021.
Vancouver:
Wierzba M. A Family of Four LRR-RLKs Modulate Development and Defense Signaling in Arabidopsis thaliana through Interaction with the Co-receptor BAK1
. [Internet] [Doctoral dissertation]. University of Arizona; 2014. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/312668.
Council of Science Editors:
Wierzba M. A Family of Four LRR-RLKs Modulate Development and Defense Signaling in Arabidopsis thaliana through Interaction with the Co-receptor BAK1
. [Doctoral Dissertation]. University of Arizona; 2014. Available from: http://hdl.handle.net/10150/312668
University of Arizona
7.
Racolta, Adriana.
The Receptor-Like Kinases GSO1, GSO2, RPK1 and TOAD2 Mediate Arabidopsis Root Patterning and Growth
.
Degree: 2013, University of Arizona
URL: http://hdl.handle.net/10150/312738
► During Arabidopsis embryogenesis, cell-cell signaling plays an essential role in establishing an organized body plan centered around two major axes of development: apical-basal and radial.…
(more)
▼ During Arabidopsis embryogenesis, cell-cell signaling plays an essential role in establishing an organized body plan centered around two major axes of development: apical-basal and radial. Two topics of great interest are how the layered structure is initiated and maintained during and after embryogenesis and how communication between layers is achieved to allow for coordinated development. Recent research involving Receptor-Like Kinases (RLKs) in plants suggests that their roles in integrating various signals are important in many aspects of development, including embryonic and post-embryonic patterning. The research presented here describes the roles of two pairs of RLKs with independent roles in two different signaling environments. The first RLK pair, GSO1 and GSO2, function in root development at the transition to photoautotrophic nutrition to integrate sugar signals and regulate root growth. GSO1 and GSO2 regulate root epidermal cell identity by controlling the pattern of cell division of stem cells. The second pair of RLKs, RPK1 and TOAD2, function to control root development by regulation of meristem proliferation and a coordinated response to signaling molecules of the CLE family. The response of wild-type roots to treatment with CLE peptides (A-type) is meristem growth arrest, resulting in short roots. toad2 mutants are insensitive to the effect of CLE peptides in reducing meristem size and TOAD2 also regulates RPK1 upon CLE stimulation. Although responding to different signals, the two pairs of RLK share a common output of regulating cell proliferation in and around the root meristem, especially in the epidermis of the root.
Advisors/Committee Members: Tax, Frans E (advisor), Fares, Hanna (committeemember), Schumaker, Karen (committeemember), Zarnescu, Daniela (committeemember).
Subjects/Keywords: Receptor-Like Kinases;
Root development;
Molecular & Cellular Biology;
Arabidopsis
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APA ·
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Manager
APA (6th Edition):
Racolta, A. (2013). The Receptor-Like Kinases GSO1, GSO2, RPK1 and TOAD2 Mediate Arabidopsis Root Patterning and Growth
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/312738
Chicago Manual of Style (16th Edition):
Racolta, Adriana. “The Receptor-Like Kinases GSO1, GSO2, RPK1 and TOAD2 Mediate Arabidopsis Root Patterning and Growth
.” 2013. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/312738.
MLA Handbook (7th Edition):
Racolta, Adriana. “The Receptor-Like Kinases GSO1, GSO2, RPK1 and TOAD2 Mediate Arabidopsis Root Patterning and Growth
.” 2013. Web. 25 Jan 2021.
Vancouver:
Racolta A. The Receptor-Like Kinases GSO1, GSO2, RPK1 and TOAD2 Mediate Arabidopsis Root Patterning and Growth
. [Internet] [Doctoral dissertation]. University of Arizona; 2013. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/312738.
Council of Science Editors:
Racolta A. The Receptor-Like Kinases GSO1, GSO2, RPK1 and TOAD2 Mediate Arabidopsis Root Patterning and Growth
. [Doctoral Dissertation]. University of Arizona; 2013. Available from: http://hdl.handle.net/10150/312738
University of Arizona
8.
Boyd, Joseph Samuel.
Eyespot Assembly and Positioning in Chlamydomonas reinhardtii
.
Degree: 2011, University of Arizona
URL: http://hdl.handle.net/10150/145298
► The eyespot of the biflagellate unicellular green alga Chlamydomonas reinhardtii is a complex organelle that facilitates directional responses of the cell to environmental light stimuli.…
(more)
▼ The eyespot of the biflagellate unicellular green alga Chlamydomonas reinhardtii is a complex organelle that facilitates directional responses of the cell to environmental light stimuli. The eyespot, which assembles de novo after every cell division and retains a distinctive association with the microtubule cytoskeleton, comprises an elliptical patch of rhodopsin photoreceptors in the plasma membrane and stacks of carotenoid-rich pigment granule arrays in the chloroplast and serves as a model for understanding how organelles are formed and placed asymmetrically in the cell. This study describes the roles of several factors in the assembly and positioning of the eyespot. Two loci, EYE2 and EYE3, define factors involved in the formation and organization of the eyespot pigment granule arrays. Whereas EYE3, a serine/threonine kinase of the ABC1 family, localizes to pigment granules, EYE2 localization corresponds to an area of the chloroplast envelope in the eyespot. These proteins play interdependent roles: EYE2 and the ChR1 photoreceptor co-position in the absence of pigment granules, and the pigment granules are required to maintain the shape and integrity of the EYE2/ChR1 patch. The miniature-eyespot locus MIN2 affects eyespot size and likely regulates the amount of material available for eyespot assembly. The MLT2 locus regulates eyespot size, number, and asymmetry. A novel locus, PEY1, modulates the position of the eyespot on the anterior-posterior axis by affecting microtubule rootlet length. A working model is developed wherein rootlet microtubule-directed photoreceptor localization establishes connections in the chloroplast envelope with EYE2, which directs the site for pigment granule array assembly, and MLT2 is proposed to negatively regulate the levels of eyespot proteins.
Advisors/Committee Members: Dieckmann, Carol L (advisor), Weinert, Ted (committeemember), Tax, Frans E. (committeemember), Nagy, Lisa (committeemember), Fares, Hanna (committeemember).
Subjects/Keywords: Chlamydomonas;
eyespot;
microtubule rootlet;
organelle biogenesis
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APA (6th Edition):
Boyd, J. S. (2011). Eyespot Assembly and Positioning in Chlamydomonas reinhardtii
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/145298
Chicago Manual of Style (16th Edition):
Boyd, Joseph Samuel. “Eyespot Assembly and Positioning in Chlamydomonas reinhardtii
.” 2011. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/145298.
MLA Handbook (7th Edition):
Boyd, Joseph Samuel. “Eyespot Assembly and Positioning in Chlamydomonas reinhardtii
.” 2011. Web. 25 Jan 2021.
Vancouver:
Boyd JS. Eyespot Assembly and Positioning in Chlamydomonas reinhardtii
. [Internet] [Doctoral dissertation]. University of Arizona; 2011. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/145298.
Council of Science Editors:
Boyd JS. Eyespot Assembly and Positioning in Chlamydomonas reinhardtii
. [Doctoral Dissertation]. University of Arizona; 2011. Available from: http://hdl.handle.net/10150/145298
University of Arizona
9.
Ganchorre, Athena Roldan.
Recognition and Respect for Difference: Science and Math Pre-service Teachers' Attributes that Underlie a Commitment to Teach in Under-resourced Schools
.
Degree: 2011, University of Arizona
URL: http://hdl.handle.net/10150/202743
► This work revealed what is at the core of a particular group of prospective teachers that underlie their commitment to teach in under-resourced schools and…
(more)
▼ This work revealed what is at the core of a particular group of prospective teachers that underlie their commitment to teach in under-resourced schools and districts. Prospective teachers committed to teaching in under-resourced schools have qualities or attributes of recognition and respect for students and families who come from low-income and culturally different backgrounds and experiences. These prospective teachers were able to recognize complex interactions that students and their families face at the individual, social and institutional level. They also sought ways to address their students' learning needs by drawing from students' experiences to make meaningful connections between home and school. To identify students' and families' lived experiences, cultural practices, and language as resources to draw from, are acts of recognition and respect towards students and their families who are, for many prospective teachers, different from themselves. Recognition and respect for difference are essential attributes that underlie a socially just and humanistic pedagogy which can positively impact the learning outcomes for students who are historically poorly served by our public schools. This work highlights a different view that prospective teachers from majority White European backgrounds have about social others. It also provides a new framework using social otherness as a lens to reveal prospective teachers' understandings and knowledge about students and families from low-income backgrounds.
Advisors/Committee Members: Tomanek, Debra (advisor), Fares, Hanna (committeemember), Nagy, Lisa (committeemember), Novodvorsky, Ingrid (committeemember), Talanquer, Vicente (committeemember), Tomanek, Debra (committeemember).
Subjects/Keywords: Respect;
Role Identity;
Social Justice;
Teacher Education;
Molecular & Cellular Biology;
Otherness;
Recognition
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Manager
APA (6th Edition):
Ganchorre, A. R. (2011). Recognition and Respect for Difference: Science and Math Pre-service Teachers' Attributes that Underlie a Commitment to Teach in Under-resourced Schools
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/202743
Chicago Manual of Style (16th Edition):
Ganchorre, Athena Roldan. “Recognition and Respect for Difference: Science and Math Pre-service Teachers' Attributes that Underlie a Commitment to Teach in Under-resourced Schools
.” 2011. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/202743.
MLA Handbook (7th Edition):
Ganchorre, Athena Roldan. “Recognition and Respect for Difference: Science and Math Pre-service Teachers' Attributes that Underlie a Commitment to Teach in Under-resourced Schools
.” 2011. Web. 25 Jan 2021.
Vancouver:
Ganchorre AR. Recognition and Respect for Difference: Science and Math Pre-service Teachers' Attributes that Underlie a Commitment to Teach in Under-resourced Schools
. [Internet] [Doctoral dissertation]. University of Arizona; 2011. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/202743.
Council of Science Editors:
Ganchorre AR. Recognition and Respect for Difference: Science and Math Pre-service Teachers' Attributes that Underlie a Commitment to Teach in Under-resourced Schools
. [Doctoral Dissertation]. University of Arizona; 2011. Available from: http://hdl.handle.net/10150/202743
University of Arizona
10.
Hart, Matthew Robert.
Understanding EGFR Modification, Trafficking, and the Importance of its Juxtamembrane Domain in Cancer
.
Degree: 2013, University of Arizona
URL: http://hdl.handle.net/10150/293476
► Much of what is known about the role of the ERBB family in cellular biology and in cancer has to do with canonical downstream signaling…
(more)
▼ Much of what is known about the role of the ERBB family in cellular biology and in cancer has to do with canonical downstream signaling cascades and modifications associated with their trafficking and degradation. The focus on canonical activity, while important, ignores a rapidly expanding number of separate, arguably equally important functions for which there is emerging knowledge. These include the translocation of ERBB family members to non-canonical sub-cellular locations including the nucleus and mitochondria. Of current interest is the elucidation of fate determination mechanisms for these proteins. How is one ERBB receptor designated to traffic to the nucleus or mitochondria, versus degradative lysosomes? A portion of the work presented here addresses the potential role of ubiquitin in EGFR nuclear translocation, a role which ubiquitin has been shown to play in the context of other proteins. This work demonstrates that while ubiquitinated EGFR can be translocated from the plasma membrane to the nucleus in response to ligand, efficient ubiquitination is not essential for this process. This work also broadens the potential roles for ubiquitin to include those involving EGFR nuclear biology. Additional work described aimed to exploit what was already known regarding the diverse roles played by the EGFR juxtamembrane domain in the non-canonical activities of EGFR and the ERBBs. This work involves the creation and evaluation of an EGFR juxtamembrane domain derived peptide designed to competitively interact with endogenous ERBB domains and inhibit their function in cancer cells. Termed EJ1, treatment induces cell death and promotes the formation of inactive ERBB dimers and reduces ERBB activation. While inactivating CaMKII signaling, myosin light chain dependent cell blebbing occurs, coincident with the induction of cell death. EJ1 also directly translocates to mitochondria, potentially contributing to a loss of mitochondrial membrane potential and production of reactive oxygen species. Finally, treatment of mouse models of breast cancer with EJ1 results in the inhibition of tumor growth and metastasis, without observable side-effects/toxicities. These data demonstrate that a portion of the ERBB juxtamembrane domain, used as an intracellular decoy, can affect tumor growth and metastasis through ERBB-dependent and ERBB-independent mechanisms, representing a novel anti-cancer therapeutic.
Advisors/Committee Members: Schroeder, Joyce A (advisor), Martinez, Jesse (committeemember), Fares, Hanna (committeemember), Gerner, Eugene (committeemember), Schroeder, Joyce A. (committeemember).
Subjects/Keywords: EGFR;
Peptide;
Ubiquitin;
Genetics;
Cancer
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APA (6th Edition):
Hart, M. R. (2013). Understanding EGFR Modification, Trafficking, and the Importance of its Juxtamembrane Domain in Cancer
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/293476
Chicago Manual of Style (16th Edition):
Hart, Matthew Robert. “Understanding EGFR Modification, Trafficking, and the Importance of its Juxtamembrane Domain in Cancer
.” 2013. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/293476.
MLA Handbook (7th Edition):
Hart, Matthew Robert. “Understanding EGFR Modification, Trafficking, and the Importance of its Juxtamembrane Domain in Cancer
.” 2013. Web. 25 Jan 2021.
Vancouver:
Hart MR. Understanding EGFR Modification, Trafficking, and the Importance of its Juxtamembrane Domain in Cancer
. [Internet] [Doctoral dissertation]. University of Arizona; 2013. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/293476.
Council of Science Editors:
Hart MR. Understanding EGFR Modification, Trafficking, and the Importance of its Juxtamembrane Domain in Cancer
. [Doctoral Dissertation]. University of Arizona; 2013. Available from: http://hdl.handle.net/10150/293476
11.
Bryan, Anthony C.
Social Networks of Receptor-like Kinases Regulate Cell Identity in Arabidopsis thaliana
.
Degree: 2011, University of Arizona
URL: http://hdl.handle.net/10150/205180
► Receptor-like kinases (RLKs) make up one of the largest gene families in Arabidopsis thaliana. These genes are required for various biological processes, including response to…
(more)
▼ Receptor-like kinases (RLKs) make up one of the largest gene families in Arabidopsis thaliana. These genes are required for various biological processes, including response to biotic stress, cell elongation, cell proliferation, and cell fate patterning. An emerging theme in Arabidopsis and other plants is that networks of RLKs are required to regulate a specific process throughout development involving spatial and temporal regulation of transcription factors. However, there are still many RLKs (>50%) with no known function.Several RLKs regulate epidermal development by contributing to early embryonic epidermal maintenance or to epidermal differentiation. In my first analysis, I characterize the role of two related RLKs GASSHO1 (GSO1) and GSO2 in epidermal differentiation. gso1 gso2 double mutants initially form an epidermis during embryogenesis, but analysis of post-embryonic root development indicates the mis-expression of epidermal-specific genes. Three previously characterized RLKs that are involved in epidermal development are also involved in meristem maintenance. In order to decipher the RLK gene networks controlling epidermal development and meristem maintenance, it is necessary to identify additional RLKs involved in both of these processes. I further identified roles for GSO1 and GSO2 in maintaining root growth and root apical meristem (RAM) activity. A future goal will be to elucidate the networks of RLKs, including GSO1 and GSO2 in regulating epidermal and RAM development.The development of the vasculature in plants is controlled by a vascular meristem, the procambium. Oriented cell divisions from the procambium produce phloem, to the periphery, and xylem, to the center of the plant. In a reverse genetic screen to determine to roles of the remaining RLKs with unknown function, we identified the RLK XYLEM INTERMIXED WITH PHLOEM1 (XIP1) that is required for vascular development. We show XIP1 is required for regulating the differentiation of the phloem and for the organization of xylem vessel elements. Our analysis indicates that XIP1 is part of a vascular meristem network, further emphasizing the importance of social networks of RLKs regulating a specific process in development.
Advisors/Committee Members: Tax, Frans E (advisor), Dieckmann, Carol (committeemember), Fares, Hanna (committeemember), Schumaker, Karen (committeemember), Weinert, Ted (committeemember), Tax, Frans E. (committeemember).
Subjects/Keywords: Development;
RLK;
Root;
Vasculature;
Molecular & Cellular Biology;
Arabidopsis;
Cell specification
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APA (6th Edition):
Bryan, A. C. (2011). Social Networks of Receptor-like Kinases Regulate Cell Identity in Arabidopsis thaliana
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/205180
Chicago Manual of Style (16th Edition):
Bryan, Anthony C. “Social Networks of Receptor-like Kinases Regulate Cell Identity in Arabidopsis thaliana
.” 2011. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/205180.
MLA Handbook (7th Edition):
Bryan, Anthony C. “Social Networks of Receptor-like Kinases Regulate Cell Identity in Arabidopsis thaliana
.” 2011. Web. 25 Jan 2021.
Vancouver:
Bryan AC. Social Networks of Receptor-like Kinases Regulate Cell Identity in Arabidopsis thaliana
. [Internet] [Doctoral dissertation]. University of Arizona; 2011. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/205180.
Council of Science Editors:
Bryan AC. Social Networks of Receptor-like Kinases Regulate Cell Identity in Arabidopsis thaliana
. [Doctoral Dissertation]. University of Arizona; 2011. Available from: http://hdl.handle.net/10150/205180
12.
Maisel, Sabrina.
The Role of Alternative Epidermal Growth Factor Receptor Trafficking in Driving Cancer Progression
.
Degree: 2017, University of Arizona
URL: http://hdl.handle.net/10150/624472
► The Epidermal Growth Factor Receptor (EGFR) is associated with a variety of cancers, including brain, lung, cervix, renal and breast. It is part of a…
(more)
▼ The Epidermal Growth Factor Receptor (EGFR) is associated with a variety of cancers, including brain, lung, cervix, renal and breast. It is part of a family of receptors known as the ErbB receptors (ErbB1/EGFR, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4), transmembrane proteins found on epithelial cells responsible for a multitude of signaling events. In cancers, EGFR is frequently mutated or improperly expressed, upregulated in more than 50 percent of basal-like cancers. Mutations commonly promote constitutive activation or increase receptor recycling. In basal-like breast cancers such as triple negative breast cancer (TNBC), named for the lack of hormone receptors (estrogen and progesterone) and the HER2 receptor, EGFR is highly upregulated and associated with a variety of oncogenic activity, including increased proliferation and migration, and inhibition of cell death. Changes in these pathways are predicated on altered trafficking and activation of EGFR, events driven by variation in stimuli and interacting partners, such as other ErbB family members or oncogenic adaptor proteins such as MUC1, a member of the mucin family. In TNBC, upon stimulus with epidermal growth factor (EGF), EGFR colocalizes with MUC1 in intracellular vesicles distributed throughout the cytoplasm. These intracellular vesicles are associated with early endosomes, as indicated by the presence of early endosome antigen 1 (EEA1). Association with MUC1 prolongs the presence of EGFR in these vesicles, as EGFR's stay is significantly reduced in cells lacking MUC1. Retention in these vesicles by MUC1 inhibits trafficking of EGFR to the lysosome for degradation and is also associated with an increase in EGF-dependent migratory ability. Introduction of late endosome inhibitors (thereby preventing lysosomal targeting) increases migration in the absence of MUC1, the same effect as in the presence of MUC1. Further, inhibition of retrograde trafficking significantly decreases the rate of migration and changes cellular distribution of filopodia corresponding to migratory ability in MUC1-containing cells. Taken together, these data indicate that MUC1 is responsible for altering EGFR trafficking by retaining EGFR in EEA1-positive vesicles for prolonged periods, allowing for increased signal transduction through retrograde trafficking of EGFR and structural reorganization promoting a migratory phenotype. Loss of the polarity protein Llgl1 is associated with alterations in EGFR trafficking, promoting highly diffuse EGFR distribution throughout the cytoplasm versus along basolateral membranes. These changes in trafficking are also associated with increases in AKT and dual-phosphorylated-ERK signal transduction, both downstream targets of activated EGFR. Altering localization of EGFR to other membranes and intracellular vesicles without inducing polarity loss through a point mutation at amino acid 667 was found to also upregulate the AKT pathway. Mislocalization driven by polarity loss or point mutation in the basolateral targeting domain is sufficient to increase…
Advisors/Committee Members: Schroeder, Joyce A (advisor), Schroeder, Joyce A. (committeemember), Briehl, Margaret (committeemember), Fares, Hanna (committeemember), Martinez, Jesse (committeemember), Wilson, Jean (committeemember).
Subjects/Keywords: epidermal growth factor receptor;
llgl1;
migration;
MUC1;
Retrograde Trafficking
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Export
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APA (6th Edition):
Maisel, S. (2017). The Role of Alternative Epidermal Growth Factor Receptor Trafficking in Driving Cancer Progression
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/624472
Chicago Manual of Style (16th Edition):
Maisel, Sabrina. “The Role of Alternative Epidermal Growth Factor Receptor Trafficking in Driving Cancer Progression
.” 2017. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/624472.
MLA Handbook (7th Edition):
Maisel, Sabrina. “The Role of Alternative Epidermal Growth Factor Receptor Trafficking in Driving Cancer Progression
.” 2017. Web. 25 Jan 2021.
Vancouver:
Maisel S. The Role of Alternative Epidermal Growth Factor Receptor Trafficking in Driving Cancer Progression
. [Internet] [Doctoral dissertation]. University of Arizona; 2017. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/624472.
Council of Science Editors:
Maisel S. The Role of Alternative Epidermal Growth Factor Receptor Trafficking in Driving Cancer Progression
. [Doctoral Dissertation]. University of Arizona; 2017. Available from: http://hdl.handle.net/10150/624472
University of Arizona
13.
Balagopal, Vidya.
STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
.
Degree: 2010, University of Arizona
URL: http://hdl.handle.net/10150/145717
► In eukaryotes, regulation of translation and decay of messenger RNA are critical for fine-tuned control of gene expression. An important point of control is the…
(more)
▼ In eukaryotes, regulation of translation and decay of messenger RNA are critical for fine-tuned control of gene expression. An important point of control is the key transition where mRNAs exit translation and assemble into a non-translating mRNP state that can accumulate in cytoplasmic granules such as P bodies and/or Stress granules. In the budding yeast Saccharomyces cerevisiae , the activators of decapping Dhh1 and Pat1 appear to promote the exit of mRNAs from translation. In my work, summarized below, I describe a new regulator of translation repression and mRNA degradation, Stm1, and its novel mode of action. First, I identified Stm1 as a novel regulator of translation repression and mRNA decay. Stm1 shows several genetic interactions with Pat1 and Dhh1, in a manner consistent with Stm1 promoting the function of Dhh1. This suggests that Stm1 has a role to play in translation repression and/or activation of mRNA decay. stm1 δ strains are defective in the degradation of a subset of mRNAs that include EDC1 and COX17 . These results strongly argue that Stm1 is a novel addition to the mRNA degradation machinery. Second, I have shown that Stm1, a known ribosome-associated protein, can bind and stall 80S ribosomes to repress translation and promote decay. Stm1 is able to repress translation and stall an 80S complex in vitro . Several mutations were identified in the protein, which link the in vitrophenotype to its biological functionin vivo. The analysis of different steps in translation reveals Stm1 functions in a novel manner to inhibit translation after the formation of an 80S complex. Since most of the regulation of translation is thought to happen at the stage of initiation, this study reveals a novel mode of translation regulation. These results also provide a direct and mechanistic link between ribosome function, inhibition of translation and the degradation of messenger RNAs.
Advisors/Committee Members: Parker, Roy (advisor), Dieckmann, Carol (committeemember), Fares, Hanna (committeemember), Weinert, Ted (committeemember), Ward, Samuel (committeemember).
Subjects/Keywords: Dhh1;
mRNA decay;
Ribosome;
Stm1;
Translation
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Balagopal, V. (2010). STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/145717
Chicago Manual of Style (16th Edition):
Balagopal, Vidya. “STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
.” 2010. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/145717.
MLA Handbook (7th Edition):
Balagopal, Vidya. “STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
.” 2010. Web. 25 Jan 2021.
Vancouver:
Balagopal V. STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
. [Internet] [Doctoral dissertation]. University of Arizona; 2010. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/145717.
Council of Science Editors:
Balagopal V. STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
. [Doctoral Dissertation]. University of Arizona; 2010. Available from: http://hdl.handle.net/10150/145717
University of Arizona
14.
Sheth, Ujwal.
Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
.
Degree: 2005, University of Arizona
URL: http://hdl.handle.net/10150/194737
► An important aspect of regulating gene expression is the interplay between mRNA translation and its degradation. In the work presented here, I, in some cases…
(more)
▼ An important aspect of regulating gene expression is the interplay between mRNA translation and its degradation. In the work presented here, I, in some cases in collaboration with others, provide insights into how mRNA translation and decay are connected and how they interact with each other to regulate gene expression. This work can be summarized as follows:First, I identified cytoplasmic processing bodies (P bodies) in yeast, which are sites where mRNAs can be decapped and degraded in a 5' to 3' manner. We base our conclusion on three key observations. First, factors involved in the 5' to 3' decay pathway accumulate in P bodies.Second, P bodies change in size when the flux of mRNA decay pathways is perturbed. For example, they decrease in size when entry into decapping is inhibited, and increase in size when decapping is blocked.Third, mRNAs trapped in the process of decay accumulate in P bodies. Second, in a collaborative effort, I have further characterized P bodies. This work involved addressing the role of RNA in P body formation and the relationship of P bodies to translation. Our results suggest that P bodies are dynamic and their size is affected by a range of cellular perturbations. We also provide evidence that P bodies are sensitive to the translational status of the cell and represent sites where translationally repressed mRNAs accumulate, and where they can be subjected to 5' to 3' decay. Third, I have determined that Nonsense-mediated decay (NMD), a quality control mechanism that rapidly degrades aberrant mRNAs, involves targeting of aberrant mRNAs to P bodies. In addition, I have identified specific roles for Upf proteins in the process of NMD: Upf1p is involved in targeting mRNAs to P bodies and Upf2p and Upf3p playing a role in degradation of the aberrant mRNAs within P bodies.The identification of P bodies has direct implications on regulation of mRNA decapping, of both normal and aberrant mRNAs. The similarities of P bodies with mRNA storage granules in other organisms imply that P bodies will play a major role in regulation of translationally repressed mRNAs.
Advisors/Committee Members: Parker, Roy (advisor), Vierling, Elizabeth (committeemember), Dieckmann, Carol (committeemember), Fares, Hanna (committeemember), Weinert, Ted (committeemember).
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sheth, U. (2005). Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/194737
Chicago Manual of Style (16th Edition):
Sheth, Ujwal. “Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
.” 2005. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/194737.
MLA Handbook (7th Edition):
Sheth, Ujwal. “Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
.” 2005. Web. 25 Jan 2021.
Vancouver:
Sheth U. Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
. [Internet] [Doctoral dissertation]. University of Arizona; 2005. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/194737.
Council of Science Editors:
Sheth U. Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
. [Doctoral Dissertation]. University of Arizona; 2005. Available from: http://hdl.handle.net/10150/194737
University of Arizona
15.
El Bejjani, Rachid Michel.
MUC1 Affects EGFR Trafficking and Signaling in Breast Cancer Cells
.
Degree: 2008, University of Arizona
URL: http://hdl.handle.net/10150/195711
► MUC1 is a large transmembrane glycoprotein that is overexpressed in about 90% of breast cancers. Importantly, MUC1 overexpression is not a mere consequence of breast…
(more)
▼ MUC1 is a large transmembrane glycoprotein that is overexpressed in about 90% of breast cancers. Importantly, MUC1 overexpression is not a mere consequence of breast tumorigenesis but can sufficiently induce breast cancer formation when overexpressed in the mammary gland. The oncogenic mechanism of MUC1 overexpression remains largely unknown. However, recent studies point towards an important role for MUC1 in signaling downstream of the epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, and a key mediator of tumorigenesis. Trafficking represents a critical aspect of MUC1 and EGFR biology, and both are endocytosed via a clathrin dependent pathway but follow different trafficking routes. While MUC1 is constitutively internalized and recycled back to the plasma membrane, EGFR is internalized in response to ligand binding and is ultimately trafficked to the lysosome to be degraded. EGFR degradation terminates its downstream signaling which when overactive can lead to cancer progression.In this work, we have demonstrated an important role for MUC1 in regulating EGFR trafficking. We showed that MUC1 expression can enhance the internalization of EGFR while inhibiting its ubiquitination. This results in a decrease in the degradation of the receptor and in an increased recycling in response to EGF. We then investigated the mechanism behind MUC1-dependent EGFR trafficking. We showed that, when MUC1 is present, EGFR colocalizes with MUC1 at the Rab11 and RME-1 positive perinuclear endocytic recycling compartment (ERC). Interestingly, MUC1 expression did not significantly alter the localization of EGFR at the Rab5-positive early endosome; However, MUC1 knockdown restored EGFR trafficking towards Rab7-positive late endosomes and away from the perinuclear ERC. These results describe a novel MUC1-dependent EGFR trafficking pathway in breast cancer cells. We investigated the effect of MUC1-dependent EGFR trafficking on EGFR signaling in cancer by analyzing tumor lysates from a Wnt-1 mouse model of breast cancer (MMTV-Wnt-1) crossed into a MUC1 overexpressing (MMFW) or a MUC1 null (WK) background. We observed an enhanced activation of ErbB1 and 2 but not ErbB3 in these tumors. This was accompanied by an increase in AKT but not MAPK pathway activation and in an increase in β-catenin and cyclinD1 expression. Taken together, our results identify MUC1 as a modulator of EGFR trafficking and describe a novel MUC1-dependent EGFR trafficking pathway. This altered EGFR trafficking results in enhanced EGFR activation and in the preferential activation of the PI3K/AKT pathway which could have significant implications for breast cancer biology and therapy.
Advisors/Committee Members: Joyce, Schdoeder A (advisor), Lance, Peter (committeemember), Fares, Hanna (committeemember), Frans, Tax (committeemember), Emmanuelle, Meuillet (committeemember).
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
El Bejjani, R. M. (2008). MUC1 Affects EGFR Trafficking and Signaling in Breast Cancer Cells
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/195711
Chicago Manual of Style (16th Edition):
El Bejjani, Rachid Michel. “MUC1 Affects EGFR Trafficking and Signaling in Breast Cancer Cells
.” 2008. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/195711.
MLA Handbook (7th Edition):
El Bejjani, Rachid Michel. “MUC1 Affects EGFR Trafficking and Signaling in Breast Cancer Cells
.” 2008. Web. 25 Jan 2021.
Vancouver:
El Bejjani RM. MUC1 Affects EGFR Trafficking and Signaling in Breast Cancer Cells
. [Internet] [Doctoral dissertation]. University of Arizona; 2008. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/195711.
Council of Science Editors:
El Bejjani RM. MUC1 Affects EGFR Trafficking and Signaling in Breast Cancer Cells
. [Doctoral Dissertation]. University of Arizona; 2008. Available from: http://hdl.handle.net/10150/195711
University of Arizona
16.
Jabbour, Maurice E.
REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
.
Degree: 2010, University of Arizona
URL: http://hdl.handle.net/10150/196151
► The activation of the immune system, particularly adaptive immunity, in response to a pathogen ( e.g. viruses) relies on complex network of cell interactions including…
(more)
▼ The activation of the immune system, particularly adaptive immunity, in response to a pathogen ( e.g. viruses) relies on complex network of cell interactions including those between lymphocytes (T cells) and dendritic cells (DC). In its simplest form, the DC-mediated activation of T cells is dependent on 1) binding of antigen presenting molecules (MHC class I and class II) and their peptides to the T cell receptor and 2) interaction between costimulatory molecules (CD80 and CD86) on DC and their receptors on T cells. Together these signaling events induce an optimal T cell-dependent immune response. Viruses, including herpesviruses and poxviruses, using evolutionarily conserved ubiquitin E3 ligases, appropriate cellular ubiquitin pathways for targeting immune molecules (CD86 or MHC), thereby evading the immune response. The notion that two evolutionarily divergent virus families share conserved ubiquitin E3 ligases suggested that viruses have acquired these enzymes from the host. Indeed, a set of cellular ubiquitin E3 ligases, termed membrane-associated RING-CH proteins (MARCH), was identified in mammalian genomes. Unlike their viral orthologs, cellular E3 ligases including MARCH proteins have regulatory functions in various cellular processes and, therefore, must be tightly controlled to prevent inadvertent effects to the host. Interestingly, due to its lymphoid-restricted expression and targeting of CD86 and MHC class II levels, MARCH1 is potentially critical for the function of DC. Furthermore, since DC are essential players in the regulation of the immune response (as evident by immune deficiencies observed following ablation of DC), MARCH1 should play a critical role in immunity. Therefore, the work presented in this thesis explores the regulation and function of MARCH1 in DC.
Advisors/Committee Members: Lybarger, Lonnie P (advisor), Lybarger, Lonnie P. (committeemember), Montfort, William R. (committeemember), Goodrum, Felicia (committeemember), Ahmad, Nafees (committeemember), Fares, Hanna (committeemember).
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jabbour, M. E. (2010). REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/196151
Chicago Manual of Style (16th Edition):
Jabbour, Maurice E. “REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
.” 2010. Doctoral Dissertation, University of Arizona. Accessed January 25, 2021.
http://hdl.handle.net/10150/196151.
MLA Handbook (7th Edition):
Jabbour, Maurice E. “REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
.” 2010. Web. 25 Jan 2021.
Vancouver:
Jabbour ME. REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
. [Internet] [Doctoral dissertation]. University of Arizona; 2010. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10150/196151.
Council of Science Editors:
Jabbour ME. REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
. [Doctoral Dissertation]. University of Arizona; 2010. Available from: http://hdl.handle.net/10150/196151
. 
Open Access Theses and Dissertations
