DOI
https://doi.org/10.25772/CST6-P368
Defense Date
2022
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Xianjun Fang
Abstract
Since its discovery in 2001, the biological functions of the highly conserved ubiquitin-like protein 5 (UBL5)/homologous to ubiquitin 1 (HUB1) have not been well characterized. Due to the lack of the characteristic C-terminal di-glycine moiety, UBL5 has been suggested to work as a regulator of protein functions, rather than a protein degrader like ubiquitin. In this study, we demonstrated that ubl5 mRNA and UBL5 protein were widely expressed in all tissues and cell lines of diverse origins. The UBL5 protein but not its mRNA was downregulated by bioenergetic stress, most likely through induction of ER stress conditions. We further explored the role of UBL5 in cell survival. First, enforced knockdown of ubl5 induced dramatic apoptosis in mammalian cell lines, suggesting that endogenous UBL5 acts as a survival factor. We next used UBL5-overexpressing cells to evaluate the role of UBL5 in protection against physiologically relevant death stimuli. Our results indicate that overexpression of UBL5 conferred resistance to ER stress-induced apoptosis, consistent with a protective role of endogenous UBL5 against ER stress-induced apoptosis. In contrast, overexpression of UBL5 did not protect against cell death induced by doxorubicin, hydrogen peroxide, or ethanol, agents that did not cause degradation of endogenous UBL5. Overall, these results identify UBL5 as an important survival factor that prevents ER stress-induced apoptosis.
Rights
© Sofiya Blat
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-4-2022