| First Author | Fang DF | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4513 | PubMed ID | 25072696 |
| Mgi Jnum | J:382132 | Mgi Id | MGI:8310390 |
| Doi | 10.1038/ncomms5513 | Citation | Fang DF, et al. (2014) NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation. Nat Commun 5:4513 |
| abstractText | 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. |
