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You searched for subject:(PTB Binding). Showing records 1 – 3 of 3 total matches.

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University of Illinois – Chicago

1. Arslan, Ahmet D. Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer.

Degree: 2012, University of Illinois – Chicago

Aberrations in alternative splicing of pre-mRNA splicing have been linked to many human malignancies, yet the mechanisms for these tumor-specific changes remain underexplored and represent a promising area for therapeutic intervention. We have reported the overexpression of a splicing factor, polypyrimidine tract-binding protein 1 (PTBP1), in ovarian tumor epithelial cells compared to matched normal controls and have further shown that PTBP1 small interfering RNA–mediated down-regulation has an antitumor effect. Coordinately, the depletion of PTBP1 expression resulted in enhanced sensitivity of ovarian tumor cells to paclitaxel and cisplatin. These data support PTBP1 as a novel target for the treatment of ovarian cancer. However, no commercially available PTBP1 inhibitors have yet been described. To expand our ability to find novel inhibitors, we developed and implemented a robust cell-based high throughput screening assay for the discovery of small molecule modulators of PTB activity. The targeting of a splicing factor, such as PTBP1, represents an innovative approach for cancer therapeutics and provides a foundation for generating new lead compounds that specifically target the PTBP1 protein to be used in ovarian cancer therapy. Advisors/Committee Members: Beck, William T. (advisor), He, Xiaolong (committee member), Mo, Yin-Yuan (committee member), Rong, Lijun (committee member), Wang, Zaijie J. (committee member).

Subjects/Keywords: PTB; Ovarian Cancer; Alternative Splicing; Cell-based High Throughput Screening; polypyrimidine tract-binding protein

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

APA (6th Edition):

Arslan, A. D. (2012). Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9337

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Arslan, Ahmet D. “Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer.” 2012. Thesis, University of Illinois – Chicago. Accessed November 29, 2020. http://hdl.handle.net/10027/9337.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Arslan, Ahmet D. “Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer.” 2012. Web. 29 Nov 2020.

Vancouver:

Arslan AD. Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer. [Internet] [Thesis]. University of Illinois – Chicago; 2012. [cited 2020 Nov 29]. Available from: http://hdl.handle.net/10027/9337.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Arslan AD. Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer. [Thesis]. University of Illinois – Chicago; 2012. Available from: http://hdl.handle.net/10027/9337

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Indian Institute of Science

2. Ramesh, V. Studies On Polypyrimidine Tract Binding Protein : Identification Of Interacting Partners.

Degree: PhD, Faculty of Science, 2010, Indian Institute of Science

PTB (HnRNP I) is a multifunctional RNA binding protein which participates in a variety of RNA metabolic processes put together called as post transcriptional gene regulation. It interacts with shuttling hnRNPs L, K and E2 of the spliceosomal machinery and also with other RNA binding proteins like PSF, Raver1 and Raver2, which assists PTB in splicing. Based on the complexity of these processes and multifunctional nature of PTB, we hypothesized that; it might interact with various additional proteins not identified till date. Keeping this objective in mind, we set out to screen the custom made 18 day old mouse testes cDNA library in pGAD10 vector available in the laboratory, to hunt for novel interacting partners of PTB using the Clontech’s Matchmaker Gal4 yeast two hybrid system III. PTB1, the prototype of PTB was chosen and the above mentioned cDNA library was screened for novel PTB interacting partners. Twenty five large scale library transformations (spanning 8*106 independent clones) were performed and 99 putatives were obtained. By re-transformation of these library plasmids with bait construct to check for the interaction phenotype and eliminating bait independent activation of reporter genes and elimination of known false positives, only 5 clones were consistent with the interaction phenotype. All these library plasmids were sequenced with vector specific primers, ORF was identified and BLAST analysis for the identification of insert was done. Two of these clones encoded the partial CDS of mouse Protein Inhibitor of Activated STAT3-PIAS3. One of these encoded the partial CDS of mouse TOLL Interacting Protein-TOLLIP. The other two encoded the partial CDS of mouse importin-α and mouse hnRNP K, both of which were already known interacting partners of PTB. GST pull down assay and mammalian matchmaker co-immunoprecipitation was used for confirming the in vitro one to one physical interaction between PTB and these newly identified protein partners. Indirect Immunofloresence was used for demonstrating the co-localization of PTB and PIAS3 in Gc1Spg mouse spermatogonial cell line. The fact that PIAS3 an E3 SUMO ligase was picked up as an interacting partner of PTB was interesting and we hypothesized that PTB might be a sumoylation substrate. Towards this, we first resorted to the prediction of sumoylation consensus motif by using SUMOPLOT. PTB indeed was found to have sumoylation consensus sites. Subsequently, in vivo sumoylation of PTB was demonstrated, where in over expression of donor protein [SUMO-1] and acceptor protein [PTB] in RAG-1 mouse kidney cell line had resulted in the identification of an approximately 67 kDa slow moving SUMO modified myc tagged PTB band apart from the bulk of unmodified 57 kDa myc-PTB. This confirmed the fact that PTB is SUMO modified only at a single consensus target site in vivo and attempts are made to map this site of modification. SUMOylation regulates diverse biological processes in vivo ranging from nucleo- cytoplasmic shuttling, alteration of protein-protein interaction, DNA… Advisors/Committee Members: Rao, M R S (advisor).

Subjects/Keywords: Proteins; Polypyrimidine Tract Binding Protein (PTB); RNA Binding Protein; Plasmid DNA; Gene Regulation; Heterogeneous Nuclear Ribonucleoprotein(HnRNP); Messenger Ribo Nucleic Acid (mRNA); Biochemistry

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

APA (6th Edition):

Ramesh, V. (2010). Studies On Polypyrimidine Tract Binding Protein : Identification Of Interacting Partners. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/659

Chicago Manual of Style (16th Edition):

Ramesh, V. “Studies On Polypyrimidine Tract Binding Protein : Identification Of Interacting Partners.” 2010. Doctoral Dissertation, Indian Institute of Science. Accessed November 29, 2020. http://etd.iisc.ac.in/handle/2005/659.

MLA Handbook (7th Edition):

Ramesh, V. “Studies On Polypyrimidine Tract Binding Protein : Identification Of Interacting Partners.” 2010. Web. 29 Nov 2020.

Vancouver:

Ramesh V. Studies On Polypyrimidine Tract Binding Protein : Identification Of Interacting Partners. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2010. [cited 2020 Nov 29]. Available from: http://etd.iisc.ac.in/handle/2005/659.

Council of Science Editors:

Ramesh V. Studies On Polypyrimidine Tract Binding Protein : Identification Of Interacting Partners. [Doctoral Dissertation]. Indian Institute of Science; 2010. Available from: http://etd.iisc.ac.in/handle/2005/659


Indian Institute of Science

3. Grover, Richa. Translational Control Of p53 And Its Isoform By Internal Initiation.

Degree: PhD, Faculty of Science, 2010, Indian Institute of Science

Tumor suppressor p53, the guardian of the genome, has been intensely studied molecule owing to its central role in maintaining cellular integrity. While the level of p53 protein is maintained low in unstressed conditions, there is a rapid increase in the functional p53 protein levels during stress conditions. It is now well documented in literature that p53 protein accumulates in the cells following DNA damage by posttranslational modifications leading to increased stability and half life of protein. Additionally, recent studies have also highlighted the significance of increased p53 translation during stress conditions. Interestingly, an alternative initiation codon has been shown to be present within the coding region of p53 mRNA. Translation initiation from this internal AUG results in an N-terminally truncated p53 isoform, described as ΔN-p53. However, the mechanisms underlying co-translational regulation of p53 and ΔN-p53 are still poorly understood. Studies have suggested that synthesis of both p53 and its ΔN-p53 isoform is regulated during cell cycle and also stress and cell-type specific manner. Interestingly, reports also demonstrate continued synthesis of both p53 isoforms during stress conditions. In contrast, global rates of cap-dependent translation initiation are shown to be reduced during stress conditions. This translation attenuation is observed mainly due to restricted availability of critical initiation factors. Interestingly, preferential synthesis of a vital pool of survival factors persists even during these circumstances. Studies have suggested that this selective translation is mediated via alternative mechanisms of translation initiation. One of the important mechanisms used for protein synthesis during these conditions is internal initiation. In this mechanism, the ribosomes are recruited to a complex RNA structural element known as ‘Internal Ribosome Entry Site (IRES)’, generally present in the 5’ untranslated region (UTR) of mRNA. Therefore, it is possible that the translation of p53 and ΔN-p53 could also be regulated by IRES mediated translation, especially during stress conditions. In this thesis the role of internal initiation in translational control of p53 and ΔN-p53 has been investigated. Additionally, the putative secondary structure of p53 IRES RNA has been determined. Further, it has been shown that polypyrimidine tract binding (PTB) protein acts as an important regulator of p53 IRES activities. The probable mechanism of action of PTB protein has also been investigated. The results suggest that interaction with PTB alters the p53 IRES conformation which could facilitate translation initiation. Finally, the possible physiological significance of existence of p53 IRES elements has been addressed. In the first part of the thesis, the presence of internal ribosome entry site within p53 mRNA has been investigated. As a first step, the 5’UTRs mediating the translation of both p53 and ΔN-p53 were cloned in the intercistronic regions of bicistronic constructs. Results of in vivo… Advisors/Committee Members: Das, Saumitra (advisor).

Subjects/Keywords: Ribonucleic Acid (RNA); Proteins; RNA Viruses; p53 Protein; p53 Protein Isoforms; p53 RNA - Structural Analysis; Protein Translation; Polypyrimidine Tract Binding Protein; Protein Regulation; IRES RNA; PTB Binding; p53 mRNA; Biochemical Genetics

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

APA (6th Edition):

Grover, R. (2010). Translational Control Of p53 And Its Isoform By Internal Initiation. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/764

Chicago Manual of Style (16th Edition):

Grover, Richa. “Translational Control Of p53 And Its Isoform By Internal Initiation.” 2010. Doctoral Dissertation, Indian Institute of Science. Accessed November 29, 2020. http://etd.iisc.ac.in/handle/2005/764.

MLA Handbook (7th Edition):

Grover, Richa. “Translational Control Of p53 And Its Isoform By Internal Initiation.” 2010. Web. 29 Nov 2020.

Vancouver:

Grover R. Translational Control Of p53 And Its Isoform By Internal Initiation. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2010. [cited 2020 Nov 29]. Available from: http://etd.iisc.ac.in/handle/2005/764.

Council of Science Editors:

Grover R. Translational Control Of p53 And Its Isoform By Internal Initiation. [Doctoral Dissertation]. Indian Institute of Science; 2010. Available from: http://etd.iisc.ac.in/handle/2005/764

.