NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation

Di-Feng Fang, Kun He, Na Wang, Zhi-Hong Sang, Xin Qiu, Guang Xu, Zhao Jian, Bing Liang, Tao Li, Hui-Yan Li, Ai-Ling Li, Tao Zhou (+5 others)
2014 Nature Communications  
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
more » ... 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.
doi:10.1038/ncomms5513 pmid:25072696 fatcat:2n7khutn6zev7mmoiqfpngl2tq