Phosphorylation and Inactivation of Myeloid Cell Leukemia 1 by JNK in Response to Oxidative Stress

Keio University, Edo, Tōkyō, Japan
Journal of Biological Chemistry (Impact Factor: 4.57). 12/2002; 277(46):43730-4. DOI: 10.1074/jbc.M207951200
Source: PubMed


Oxidative stress induces JNK activation, which leads to apoptosis through mitochondria-dependent caspase activation. However, little is known about the mechanism by which JNK alters mitochondrial function. In this study, we investigated the role of phosphorylation of myeloid cell leukemia 1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family, in oxidative stress-induced apoptosis. We found that JNK phosphorylated Ser-121 and Thr-163 of Mcl-1 in response to stimulation with H(2)O(2) and that transfection of unphosphorylatable Mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with H(2)O(2). JNK-dependent phosphorylation and thus inactivation of Mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.

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Available from: Akihiro Umezawa, Jun 19, 2014
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    • "The critical role of ASK1 in apoptosis induction has been reported [36-38]. We have found that BSO triggers activation of ASK1 in ATO-treated cells. "
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    • "Its interactions with other Bcl-2 family members can favour its stabilization or its degradation, depending of the partner [17]. Mcl-1 degradation can involve the proteasome pathway following JNK and GSK3 associated Mcl-1 phosphorylations [18], but can also be a consequence of caspases activity [19]. This last possibility has been excluded in our model since Mcl-1 was decreased even in condition in which apoptosis is not detected (24 h). "
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