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Publication : MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress.

First Author  Xia Y Year  2007
Journal  Mol Cell Biol Volume  27
Issue  2 Pages  510-7
PubMed ID  17101801 Mgi Jnum  J:117692
Mgi Id  MGI:3697264 Doi  10.1128/MCB.01355-06
Citation  Xia Y, et al. (2007) MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress. Mol Cell Biol 27(2):510-7
abstractText  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.
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