NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation

被引：37

作者：

Fang, Di-Feng ^{[1
]}

He, Kun ^{[1
]}

Wang, Na ^{[1
]}

Sang, Zhi-Hong ^{[1
]}

Qiu, Xin ^{[1
]}

Xu, Guang ^{[1
]}

Jian, Zhao ^{[1
]}

Liang, Bing ^{[1
]}

Li, Tao ^{[1
]}

Li, Hui-Yan ^{[1
]}

Li, Ai-Ling ^{[1
]}

Zhou, Tao ^{[1
]}

Gong, Wei-Li ^{[1
]}

Yang, Baoli ^{[2
]}

Karin, Michael ^{[3
,4
]}

Zhang, Xue-Min ^{[1
]}

Li, Wei-Hua ^{[1
]}

机构：

[1] Inst Basic Med Sci, Natl Ctr Biomed Anal, State Key Lab Prote, Beijing 100850, Peoples R China

[2] Univ Iowa, Dept Obstet & Gynecol, Carver Coll Med, Iowa City, IA 52242 USA

[3] Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Ctr Canc, Dept Pharmacol, San Diego, CA 93093 USA

[4] Univ Calif San Diego, Dept Pathol, San Diego, CA 93093 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

PHOSPHATIDYLINOSITOL; 3-KINASE; IMMUNE-RESPONSE; LIGASE; RECOMBINATION; STABILITY; MECHANISM; COMPLEX; GROWTH; ROLES; PTEN;

D O I：

10.1038/ncomms5513

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：

CD40, a member of tumour necrosis factor receptor (TNFR) superfamily, has a pivotal role in B-cell-mediated immunity through various effector pathways including AKT kinase, but the signal transduction of CD40-meidated AKT activation is poorly understood. Here we report that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4), homologous to E6-AP Carboxyl Terminus family E3 ubiquitin ligase, is a novel component of the CD40 signalling complex. It has a key role in CD40-mediated AKT activation and is involved in modulating immunoglobulin class switch through regulating the expression of activation-induced cytidine deaminase. NEDD4 constitutively interacts with CD40 and mediates K63-linked ubiquitination of TNFR-associated factor3 (TRAF3). The ubiquitination of TRAF3 by NEDD4 is critical for CD40-mediated AKT activation. Thus, NEDD4 is a previously unknown component of the CD40 signalling complex necessary for AKT activation.

引用

页数：11

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