Please use this identifier to cite or link to this item:
Title: Promising Molecular Modulations of E3 Ubiquitin Ligases Regulate Cellular Proliferation and Suppresses Misfolded Proteins Accumulation
Researcher : Joshi, Vibhuti
Supervisor: Mishra, Amit Kumar
Department: Bioscience and Bioengineering
Issue Date: Jul-2018
Citation: Joshi, Vibhuti. (2019). Promising Molecular Modulations of E3 Ubiquitin Ligases Regulate Cellular Proliferation and Suppresses Misfolded Proteins Accumulation (Doctor's thesis). Indian Institute of Technology Jodhpur, Jodhpur.
Abstract: Cellular protein quality control mechanisms always present a continuous and rigorous check over all intracellular proteins before they can participate in various physiological processes with the help of cellular proteolytic pathways like autophagy and ubiquitin-proteasome system (UPS). E3 ubiquitin ligases are a major component of UPS and play a crucial role in diseases like cancer and neurodegeneration. The UPS employs a few E3 ubiquitin ligases for the intracellular degradation of cyclin-dependent kinase inhibitor 1B/ p27 kip1 that tightly controls cell cycle progression and may function as biomarkers in various cancers. The current study demonstrated that glycoprotein Gp78, a putative E3 ubiquitin ligase, is involved in the stabilization of intracellular levels of p27. Gp78 increases the accumulation of both phosphorylated and unphosphorylated forms of p27 in cells. Overall, it suggests a valuable multifactorial regulatory mechanism and linkage of p27 with UPS pathway and its components. Major neurodegenerative disorders are characterized by the formation of misfolded proteins aggregates inside or outside the cells. E3 ubiquitin ligases are associated with multiple neurobiological mechanisms and degradation of these aggregates. The present study found Myricetin, a natural molecule (flavonoid) as a modulator of E3 ubiquitin ligases, which can eliminate various misfolded proteins via modulating levels of Hsp70 chaperone and E3 ubiquitin ligase E6-AP. Results suggest that Myricetin treatment suppresses the aggregation of different aberrant proteins associated with neurodegeneration and reduce cytotoxicity. Thus, it provides a new mechanistic and therapeutic insight based on small molecule-mediated regulations of disturbed protein quality control mechanism, to maintain the state of proteostasis.
Pagination: xii, 88p.
Accession No.: TP00036
Appears in Collections:Ph. D. Theses

Files in This Item:
File Description SizeFormat 
TP00036.pdf6.35 MBAdobe PDFView/Open    Request a copy
01_declaration.pdf81.05 kBAdobe PDFView/Open
02_certificate.pdf135.96 kBAdobe PDFView/Open
03_title.pdf182 kBAdobe PDFView/Open
04_abstract.pdf35.24 kBAdobe PDFView/Open
05_acknowledgements.pdf66.77 kBAdobe PDFView/Open
06_contents.pdf346.7 kBAdobe PDFView/Open
07_list_of_figures.pdf406.06 kBAdobe PDFView/Open
08_list_of_tables.pdf34.37 kBAdobe PDFView/Open
09_list_of_symbols.pdf206.8 kBAdobe PDFView/Open
10_list_of_abbreviations.pdf209.59 kBAdobe PDFView/Open
11_chapter 1.pdf137.64 kBAdobe PDFView/Open
12_chapter 2.pdf1.32 MBAdobe PDFView/Open
13_chapter 3.pdf3.19 MBAdobe PDFView/Open
14_chapter 4.pdf2.89 MBAdobe PDFView/Open
15_chapter 5 summary and conclusions.pdf104.99 kBAdobe PDFView/Open
16_annexure A.pdf331.93 kBAdobe PDFView/Open
17_references.pdf206.91 kBAdobe PDFView/Open

Items in IIT Jodhpur Theses Repository are protected by copyright, with all rights reserved, unless otherwise indicated.