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Date of Award
5-2009
Access Type
Campus Access
Document type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Animal Biotechnology and Biomedical Sciences
First Advisor
Barbara A. Osborne
Second Advisor
Juan Anguita
Third Advisor
Pablo Visconti
Subject Categories
Cell Biology | Molecular Biology
Abstract
Nur77, an orphan nuclear receptor, plays a key role in T cell apoptosis. As a transcription factor, Nur77 is assumed to exert its functions by driving the expression of target genes. However, Nur77 targets in T cell apoptosis are unknown. In cancer cell lines, Nur77 can induce apoptosis through the intrinsic apoptotic pathway but it remains controversial how Nur77 kills T cells. In this study, we provide biochemical, pharmacological and genetic evidence demonstrating that Nur77 induces apoptosis through the activation of the intrinsic pathway in T cells. We also show that Nur77 is a physiological substrate of the MEK-ERK-RSK-cascade. Specifically, we demonstrate that RSK phosphorylate Nur77 at serine 354 and this modulates Nur77 nuclear export and intracellular translocation during T cell death. Our data reveal that Nur77 phosphorylation and mitochondrial targeting, regulated by RSK, may define a role for the MEK1/2-ERK1/2 cascade in T cell apoptosis.
DOI
https://doi.org/10.7275/5649950
Recommended Citation
Wang, Aibo, "Phosphorylation Of Nur77 By MEK-ERK-RSK Cascade Induces Mitochondrial Translocation And Apoptosis In T Cells" (2009). Doctoral Dissertations 1896 - February 2014. 97.
https://doi.org/10.7275/5649950
https://scholarworks.umass.edu/dissertations_1/97