Phosphorylation of Caspase-8 (Thr-263) by Ribosomal S6 Kinase 2 (RSK2) Mediates Caspase-8 Ubiquitination and Stability

被引：43

作者：

Peng, Cong ^{[1
]}

Cho, Yong-Yeon ^{[1
]}

Zhu, Feng ^{[1
]}

Zhang, Jishuai ^{[1
]}

Wen, Weihong ^{[1
]}

Xu, Yanming ^{[1
]}

Yao, Ke ^{[1
]}

Ma, Wei-Ya ^{[1
]}

Bode, Ann M. ^{[1
]}

Dong, Zigang ^{[1
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 09期

基金：

美国国家卫生研究院;

关键词：

PROTEIN LIGASE; CELL-SURVIVAL; HISTONE H3; APOPTOSIS; ACTIVATION; PATHWAY; GROWTH; TRANSFORMATION; DEGRADATION; REQUIREMENT;

D O I：

10.1074/jbc.M110.172338

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability. Finally, RSK2 blocks Fas-induced apoptosis through its phosphorylation of caspase-8. These data provide a direct link between RSK2 and caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by RSK2.

引用

页码：6946 / 6954

页数：9

共 27 条

[21] Executioner caspase-3,-6, and-7 perform distinct, non-redundant roles during the demolition phase of apoptosis [J].