JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD

被引：325

作者：

Yu, CF ^{[1
]}

Minemoto, Y ^{[1
]}

Zhang, JY ^{[1
]}

Liu, J ^{[1
]}

Tang, FM ^{[1
]}

Bui, TN ^{[1
]}

Xiang, JL ^{[1
]}

Lin, AN ^{[1
]}

机构：

[1] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA

来源：

MOLECULAR CELL | 2004年 / 13卷 / 03期

关键词：

D O I：

10.1016/S1097-2765(04)00028-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

JNK has been suggested to be proapoptotic, antiapoptotic, or have no role in apoptosis depending on the cell type and stimulus used. The precise mechanism of JNK action, under conditions when it promotes cell survival, is not entirely clear. Here, we report that JNK is required for IL-3-mediated cell survival through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein BAD. IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but suppressed by expression of a constitutively active JNK. JNK phosphorylates BAD at threonine 201, thereby inhibiting BAD association with the antiapoptotic molecule BCL-X-L. IL-3 induces BAD phosphorylation at threonine 201, and replacement of threonine 201 by alanine generates a BAD mutant, which promotes IL-3 withdrawal-induced apoptosis. Thus, our results provide a molecular mechanism by which JNK contributes to cell survival.

引用

页码：329 / 340

页数：12

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