TY - JOUR
T1 - MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress
AU - Xia, Yan
AU - Wang, Ji
AU - Xu, Shuichan
AU - Johnson, Gary L.
AU - Hunter, Tony
AU - Lu, Zhimin
PY - 2007/1
Y1 - 2007/1
N2 - 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 downregnlated 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 downregnlatioE of c-Jun promotes apoptosis.
AB - 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 downregnlated 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 downregnlatioE of c-Jun promotes apoptosis.
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U2 - 10.1128/MCB.01355-06
DO - 10.1128/MCB.01355-06
M3 - Article
C2 - 17101801
AN - SCOPUS:33846130923
SN - 0270-7306
VL - 27
SP - 510
EP - 517
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 2
ER -