The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation

被引：514

作者：

Yang, Wei-Lei ^{[1
,2
]}

Wang, Jing ^{[1
]}

Chan, Chia-Hsin ^{[1
]}

Lee, Szu-Wei ^{[1
,2
]}

Campos, Alejandro D. ^{[3
]}

Lamothe, Betty ^{[3
]}

Hur, Lana ^{[3
]}

Grabiner, Brian C. ^{[1
,2
]}

Lin, Xin ^{[1
,2
]}

Darnay, Bryant G. ^{[3
]}

Lin, Hui-Kuan ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[2] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

来源：

SCIENCE | 2009年 / 325卷 / 5944期

关键词：

HUMAN CANCER; PH DOMAIN; PATHWAY; MDM2; SURVIVAL; RECEPTOR;

D O I：

10.1126/science.1175065

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Akt signaling plays a central role in many biological functions, such as cell proliferation and apoptosis. Because Akt (also known as protein kinase B) resides primarily in the cytosol, it is not known how these signaling molecules are recruited to the plasma membrane and subsequently activated by growth factor stimuli. We found that the protein kinase Akt undergoes lysine-63 chain ubiquitination, which is important for Akt membrane localization and phosphorylation. TRAF6 was found to be a direct E3 ligase for Akt and was essential for Akt ubiquitination, membrane recruitment, and phosphorylation upon growth-factor stimulation. The human cancer-associated Akt mutant displayed an increase in Akt ubiquitination, in turn contributing to the enhancement of Akt membrane localization and phosphorylation. Thus, Akt ubiquitination is an important step for oncogenic Akt activation.

引用

页码：1134 / 1138

页数：5