Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Xianjun Fang
Abstract
Ubiquitin-like Protein 5 (UBL5) is unique compared to other ubiquitin-like proteins due to its C-terminal di-Tyrosine moiety, which allows for non-covalent targeting, non-degrading regulation of other proteins. UBL5 is evolutionarily conserved across mammals, and is widely expressed across different organs and cell lines. Previous studies show that UBL5 is involved in regulation of pre-RNA splicing and functional integrity of the Fanconi anemia DNA repair pathway. The Fang lab has created a conditional liver-specific UBL5 knockout mouse model to study the role of UBL5 in cellular metabolism and metabolic diseases. In the present study, we discovered a novel function of UBL5 in regulation of glycogen homeostasis. Loss of UBL5 dramatically increases glycogen accumulation in the liver of mice or in cell lines of liver origin. RNA-Seq data analysis indicated that the depletion of UBL5 downregulates glycogenolytic enzymes, such as glycogen phosphorylase L, phosphoglucomutase 1, and the lysosomal acid α-glucosidase. We also found the loss of UBL5 leads to the downregulation of Laforin and upregulation of Malin, which can potentially contribute to the hyperphosphorylation and accumulation of glycogen. We further showed the impact of UBL5 depletion on astrocytes of the brain, another glycogen-storing tissue/cell type. These findings together reveal a novel function of endogenous UBL5 in prevention of abnormal glycogen storage. Further studies are needed to understand the mechanistic details and functional consequences of the role of UBL5 in glycogen regulation.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-30-2026