Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

被引：25

作者：

Zhang, J. ^{[1
]}

Zhu, F. ^{[1
]}

Li, X. ^{[1
,2
]}

Dong, Z. ^{[1
,2
]}

Xu, Y. ^{[1
]}

Peng, C. ^{[1
]}

Li, S. ^{[1
]}

Cho, Y-Y ^{[1
,3
]}

Yao, K. ^{[1
]}

Zykova, T. A. ^{[1
]}

Bode, A. M. ^{[1
]}

Dong, Z. ^{[1
,2
]}

机构：

[1] Univ Minnesota, Hormel Inst, Dept Cellular & Mol Biol, 801 16th Ave NE, Austin, MN 55912 USA

[2] Zhengzhou Univ, Basic Med Sch, Zhengzhou, Peoples R China

[3] Catholic Univ Korea, Coll Pharm, Gyeonggi Do, South Korea

来源：

ONCOGENE | 2012年 / 31卷 / 14期

基金：

美国国家卫生研究院;

关键词：

cell transformation; Rack1; c-Jun; phosphorylation; degradation; UBIQUITIN LIGASE; JNK; RAS; AP-1; RECOGNITION; ACTIVATION; RECEPTOR; TARGETS;

D O I：

10.1038/onc.2011.369

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 c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases. Oncogene (2012) 31, 1835-1844; doi: 10.1038/onc.2011.369; published online 22 August 2011

引用

页码：1835 / 1844

页数：10

共 36 条

[1] RACK1 is up-regulated in angiogenesis and human carcinomas [J].