Document Detail

MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress.
MedLine Citation:
PMID:  17101801     Owner:  NLM     Status:  MEDLINE    
c-Jun, a major transcription factor in the activating protein 1 family of regulatory proteins, is activated by many physiologic and pathological stimuli. We show here that c-Jun was downregulated in response to osmotic stress via ubiquitination-dependent degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activity toward c-Jun in vitro and in vivo. The reduced c-Jun protein level resulting from exogenous expression of wild-type MEKK1 and the opposite effect induced by expression of a MEKK1 PHD/RING finger domain mutant were consistent with a higher level of c-Jun protein in MEKK1(-/-) cells than in corresponding wild-type cells. The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun in response to osmotic stress. Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis.
Yan Xia; Ji Wang; Shuichan Xu; Gary L Johnson; Tony Hunter; Zhimin Lu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-13
Journal Detail:
Title:  Molecular and cellular biology     Volume:  27     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-01     Completed Date:  2007-02-05     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  510-7     Citation Subset:  IM    
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MeSH Terms
Cell Line
MAP Kinase Kinase Kinase 1 / genetics,  physiology*
Mitogen-Activated Protein Kinase 8 / metabolism
Osmotic Pressure
Proteasome Endopeptidase Complex / physiology
Protein Structure, Tertiary
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
Ubiquitin-Protein Ligases / metabolism*
Grant Support
1R01 CA 109035-01A1/CA/NCI NIH HHS; CA 16672/CA/NCI NIH HHS; CA 55418/CA/NCI NIH HHS; CA 82683/CA/NCI NIH HHS; R01 CA109035/CA/NCI NIH HHS
Reg. No./Substance:
0/Proto-Oncogene Proteins c-jun; EC Protein Kinase 8; EC Kinase Kinase Kinase 1; EC Endopeptidase Complex; EC Ligases

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