Dissertation/Thesis Abstract

Characterization of GIV-GRP78 Interaction during Endoplasmic Reticulum Stress: A Promising Target to Curb Cancer Cell Survival
by Limso, Clariss Ann Ann Lee, M.S., California State University, Long Beach, 2019, 79; 13859734
Abstract (Summary)

Endoplasmic Reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. Cells facing ER stress initially attempt to restore cellular homeostasis, but if the stress becomes chronic and homeostasis is not achieved within a reasonable timeframe, cells initiate programmed cell death. Cancer cells are able to withstand and survive ER stress better than regular cells. Overexpression of the chaperone Glucose Regulated Protein 78 kDa (GRP78) is one of the key factors that promote cancer cell survival during ER stress. Although it is an ER resident protein, recent studies have shown that when overexpressed, GRP78 can translocate to other cellular locations. In cancer, GRP78 is translocated to the cell surface from where it can activate cytoprotective signals; however, the mechanism by which it does so remains elusive. Our laboratory has recently identified Gα-Interacting Vesicle associated protein (GIV)—a known enhancer of pro-survival signaling—as a novel binding partner of GRP78. Here, we characterized the biochemical and spatiotemporal aspects of the GIV-GRP78 interaction. First, we mapped the GIV binding region on GRP78 and demonstrated the interaction between endogenous GIV and GRP78 under ER stress conditions. We also identified the sub-cellular locations where the two proteins can interact during ER stress. Finally, we showed that depletion of GIV reduced the cell surface translocation of GRP78 during ER stress, suggesting the possible cellular role for this interaction. Taken together, this work has identified GIV-GRP78 interaction as a potential target to reduce cancer cell viability in the face of ER stress, and will be valuable for research to further delineate the mechanisms involved in cancer cell survival during chronic ER stress.

Indexing (document details)
Advisor: Bhandari, Deepali
Commitee: Gharakhanian, Editte, Schwans, Jason
School: California State University, Long Beach
Department: Chemistry and Biochemistry
School Location: United States -- California
Source: MAI 81/1(E), Masters Abstracts International
Subjects: Biochemistry, Oncology
Keywords: GIV-GRP78, Endoplasmic reticulum stress, Cancer cell
Publication Number: 13859734
ISBN: 9781085558648
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