Abstract/Details

Phosphorylation of Nur77 by MEL-ERK-RSK cascade induces mitochondrial translocation and apoptosis in T cells


2009 2009

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Abstract (summary)

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.

Indexing (details)


Subject
Molecular biology;
Cellular biology
Classification
0307: Molecular biology
0379: Cellular biology
Identifier / keyword
Biological sciences; Apoptosis; MAP kinase; Mitochondria; Mitochondrial translocation; Nur77; Phosphorylation; T cells
Title
Phosphorylation of Nur77 by MEL-ERK-RSK cascade induces mitochondrial translocation and apoptosis in T cells
Author
Wang, Aibo
Number of pages
107
Publication year
2009
Degree date
2009
School code
0118
Source
DAI-B 70/09, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109352252
Advisor
Osborne, Barbara A.
Committee member
Anguita, Juan; Nambu, JOhn; Visconti, Pablo
University/institution
University of Massachusetts Amherst
Department
Animal Science
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3372283
ProQuest document ID
304921806
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304921806
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