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You searched for +publisher:"U of Massachusetts : Med" +contributor:("Elliot J. Androphy, M.D."). Showing records 1 – 3 of 3 total matches.

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1. Melanson, Suzanne Marie. Functional Interaction of BPV-1 E2 with the Papillomavirus Genome: A Dissertation.

Degree: Immunology and Microbiology, Department of Medicine, 2009, U of Massachusetts : Med

The bovine papillomavirus type 1 E2 protein is a multifunctional early viral protein with roles in all phases of the cell cycle. E2 is required during G1 as a transcription factor, in S phase to initiate viral replication and during mitosis to tether the viral genome to dividing DNA. The viral genome contains 17 E2 binding sites, the majority of which are concentrated in the long control region (LCR), a regulatory region that is upstream of the viral coding sequence. The role of these binding sites has been explored in vitro using small plasmids and E1 and E2 proteins expressed in bacteria and insect cells. In this study we attempt to examine the placement of E2 on its binding sites during all phases of the cell cycle and in the context of a stably replicating viral system. As part of the examination of the role of E2 during mitosis, we have also examined the role of the cohesin protein Scc1 in viral tethering. Two groups have published disparate reports identifying the cellular protein that binds to the transactivation domain of E2 to stably maintain viral genomes during cell division. Our group has published that it is the DNA helicase ChlR1 that is required for viral tethering, while it has been reported that it is the bromodomain protein Brd4 that is responsible. In this study we contribute to a report that shows that the cellular protein Scc1 binds to the viral genome through a ChlR1 independent mechanism. The cohesin protein binds to BPV-1 E2 at intermittent stages of the cell cycle and may be a factor in viral genome tethering. This interaction may also be important for regulating viral transcription. Advisors/Committee Members: Elliot J. Androphy, M.D..

Subjects/Keywords: DNA-Binding Proteins; Nuclear Proteins; Transcription Factors; Viral Proteins; Bovine papillomavirus; Amino Acids, Peptides, and Proteins; Cells; Genetic Phenomena; Viruses

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Melanson, S. M. (2009). Functional Interaction of BPV-1 E2 with the Papillomavirus Genome: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/410

Chicago Manual of Style (16th Edition):

Melanson, Suzanne Marie. “Functional Interaction of BPV-1 E2 with the Papillomavirus Genome: A Dissertation.” 2009. Doctoral Dissertation, U of Massachusetts : Med. Accessed July 06, 2020. https://escholarship.umassmed.edu/gsbs_diss/410.

MLA Handbook (7th Edition):

Melanson, Suzanne Marie. “Functional Interaction of BPV-1 E2 with the Papillomavirus Genome: A Dissertation.” 2009. Web. 06 Jul 2020.

Vancouver:

Melanson SM. Functional Interaction of BPV-1 E2 with the Papillomavirus Genome: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2009. [cited 2020 Jul 06]. Available from: https://escholarship.umassmed.edu/gsbs_diss/410.

Council of Science Editors:

Melanson SM. Functional Interaction of BPV-1 E2 with the Papillomavirus Genome: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2009. Available from: https://escholarship.umassmed.edu/gsbs_diss/410

2. Evans, Matthew C. Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels.

Degree: Interdisciplinary Graduate Program, Medicine, 2011, U of Massachusetts : Med

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder that is the leading genetic cause of infantile death. SMA is caused by homozygous deletion or mutation of the survival of motor neuron 1 gene (SMN1). The SMN2 gene is nearly identical to SMN1, however is alternatively spliced. The close relationship to SMN1 results in SMN2 being a very power genetic modifier of SMA disease severity and a target for therapies. In this study we attempt to characterize novel chemical compounds identified as potential activators of the SMN2 gene. Additionally, we sought to determine the regulatory role individual HDAC proteins use to control expression of full length protein from the SMN2 gene. We used quantitative PCR to determine the effects of novel compounds and shRNA silencing of individual HDACs on the steady state levels of a SMN2-luciferase reporter transcripts. We determined that the compounds identified in multiple reporter high throughput screens increased SMN protein levels via transcriptional activation of the SMN2 gene. Other compounds identified in the same screen functioned post-transcriptionally, possibly stabilizing the SMN protein itself by decreasing degradation. Furthermore, we determined that reduction of individual HDAC proteins was sufficient to increase SMN protein levels in a transgenic reporter system. Knockdown of class I HDAC proteins preferentially activated the reporter by increased promoter transcription. Silencing of class II HDAC proteins maintained transcriptional activity; however silencing of HDAC 5 and 6 also appeared to enhance inclusion of an alternatively spliced exon. This collective work defines a quantitative RNA based protocol to determine mechanism of SMN reporter increase in response to any chosen treatment method. Additionally, this work highlights HDAC proteins 2 and 6 as excellent investigative targets. These data are important to the basic understanding of SMN expression regulation and the refinements of current therapeutic compounds as well as the development of novel SMA therapeutics. Advisors/Committee Members: Elliot J. Androphy, M.D..

Subjects/Keywords: Muscular Atrophy; Spinal; Survival of Motor Neuron 2 Protein; Histone Deacetylases; Amino Acids, Peptides, and Proteins; Enzymes and Coenzymes; Nervous System Diseases; Neuroscience and Neurobiology; Nucleic Acids, Nucleotides, and Nucleosides; Pathological Conditions, Signs and Symptoms

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Evans, M. C. (2011). Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/566

Chicago Manual of Style (16th Edition):

Evans, Matthew C. “Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels.” 2011. Doctoral Dissertation, U of Massachusetts : Med. Accessed July 06, 2020. https://escholarship.umassmed.edu/gsbs_diss/566.

MLA Handbook (7th Edition):

Evans, Matthew C. “Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels.” 2011. Web. 06 Jul 2020.

Vancouver:

Evans MC. Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2011. [cited 2020 Jul 06]. Available from: https://escholarship.umassmed.edu/gsbs_diss/566.

Council of Science Editors:

Evans MC. Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels. [Doctoral Dissertation]. U of Massachusetts : Med; 2011. Available from: https://escholarship.umassmed.edu/gsbs_diss/566

3. Quinlan, Edward J. Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation.

Degree: Immunology and Microbiology, Medicine, 2012, U of Massachusetts : Med

Human papillomavirus infection is the cause of more than 99% of cervical cancer cases. The current vaccine is ineffective therapeutically; highlighting the need for continued papillomavirus research. One avenue that could be explored in this regard is the function of the papillomavirus E2 regulatory proteins. HPV E2 represses expression of the viral E6 and E7 oncoproteins. Reintroduction of E2 into cervical carcinoma cells results in growth arrest and cellular senescence. Understanding the mechanism of how E2 regulates the early promoter may be key to developing new therapeutic and prophylactic vaccines. Here, we describe regulation of E2 through acetylation and possibly through direct interaction with a novel cellular interacting protein, RINT1. Histone acetyltransferase (HAT) proteins have been demonstrated to interact with Bovine Papillomavirus (BPV) and Human Papillomavirus (HPV) E2 proteins as well as enhance E2 dependant transcription luciferase reporter plasmid containing E2 binding sites. We demonstrate that HATs p300, CBP, and pCAF are limiting for E2 dependant transcriptional activation and that each protein functions independently. We have also identified that BPV-1 E2 is a substrate for acetylation by p300. Mutants of E2 that cannot be acetylated on lysines 111 or 112, display abnormal transcriptional phenotypes. Cells deficient in p300 display similar transcriptional defects that are intensified by CBP depletion. We propose that acetylation of BPV-1 E2 is necessary for transcriptional activation. Acetylation generates a binding site through which a co-factor may interact via a bromodomain. Regulation of E2 dependent transcriptional activation through a post-transcriptional modification represents a novel method through which BPV-1 controls gene expression. We also present evidence for a direct interaction between BPV-1 E2 and the cellular factor RINT1. This interaction does not appear to be critical for transcriptional regulation; however, several other functional pathways are indicated by the cellular complexes in which RINT1 functions. Some of these, such as ER/Golgi vesicular transport and hTERT independent telomere maintenance, are pathways in which E2 has no known role. Further investigation into regulation and consequences of E2 acetylation and the biological significance of the interaction between E2 and RINT1 could prove important in understanding the complex role of E2 in papillomavirus infection. Advisors/Committee Members: Elliot J. Androphy, M.D..

Subjects/Keywords: DNA-Binding Proteins; Viral Proteins; Bovine papillomavirus 1; Alphapapillomavirus; Acetylation; Cell Cycle Proteins; Amino Acids, Peptides, and Proteins; Biochemical Phenomena, Metabolism, and Nutrition; Cells; Environmental Public Health; Genetic Phenomena; Immunology and Infectious Disease; Investigative Techniques; Neoplasms; Therapeutics; Virology; Viruses

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Quinlan, E. J. (2012). Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/585

Chicago Manual of Style (16th Edition):

Quinlan, Edward J. “Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation.” 2012. Doctoral Dissertation, U of Massachusetts : Med. Accessed July 06, 2020. https://escholarship.umassmed.edu/gsbs_diss/585.

MLA Handbook (7th Edition):

Quinlan, Edward J. “Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation.” 2012. Web. 06 Jul 2020.

Vancouver:

Quinlan EJ. Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2012. [cited 2020 Jul 06]. Available from: https://escholarship.umassmed.edu/gsbs_diss/585.

Council of Science Editors:

Quinlan EJ. Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2012. Available from: https://escholarship.umassmed.edu/gsbs_diss/585

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