Document Detail


Jun proteins are starvation-regulated inhibitors of autophagy.
MedLine Citation:
PMID:  20197466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The growing number of biological functions affected by autophagy ascribes a special significance to identification of factors regulating it. The activator protein-1 (AP-1) transcription factors are involved in most aspects of cellular proliferation, death, or survival, yet no information regarding their involvement in autophagy is available. Here, we show that the AP-1 proteins JunB and c-Jun, but not JunD, c-Fos, or Fra-1, inhibit autophagy. JunB inhibits autophagy induced by starvation, overexpression of a short form of ARF (smARF), a potent inducer of autophagy, or even after rapamycin treatment. In agreement, acute repression of JunB expression, by JunB knockdown, potently induces autophagy. As expected from autophagy-inhibiting proteins, Jun B and c-Jun expression is reduced by starvation. Decrease in JunB mRNA expression and posttranscriptional events downregulate JunB protein expression after starvation. The inhibition of autophagy by JunB is not mediated by mammalian target of rapamycin (mTOR) regulation, as it occurs also in the absence of mTOR activity, and autophagy induced by JunB knockdown is not correlated with changes in mTOR activity. Nevertheless, the transcriptional activities of c-Jun and JunB are required for autophagy inhibition, and JunB incapable of heterodimerizing is a less effective inhibitor of autophagy. Most importantly, inhibition of autophagy in starved HeLa cells by JunB enhances apoptotic cell death. We suggest that JunB and c-Jun are regulators of autophagy whose expression responds to autophagy-inducing signals.
Authors:
Orli Yogev; Rachel Goldberg; Shira Anzi; Ohad Yogev; Eitan Shaulian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-02
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-16     Completed Date:  2010-04-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2318-27     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy / physiology*
Down-Regulation
Hela Cells
Humans
Intracellular Signaling Peptides and Proteins / genetics,  metabolism,  physiology
Mice
Protein-Serine-Threonine Kinases / genetics,  metabolism,  physiology
Proto-Oncogene Proteins c-jun / genetics,  metabolism,  physiology*
Transcription Factor AP-1 / genetics,  metabolism,  physiology
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases

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