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; Wei-Li Gong; Baoli Yang; Michael Karin; Xue-Min Zhang; Wei-Hua Li

doi:10.1038/ncomms5513

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NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.5(1), pp.4513-4513

07/29/2014

DOI: 10.1038/ncomms5513

PMID: 25072696

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Abstract

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.

Flow Cytometry

Immunoprecipitation

Mass Spectrometry

Humans

Endosomal Sorting Complexes Required for Transport - metabolism

Ubiquitin-Protein Ligases - metabolism

TNF Receptor-Associated Factor 3 - metabolism

Reverse Transcriptase Polymerase Chain Reaction

Mice, Knockout

Immunity, Cellular - immunology

Signal Transduction - immunology

Ubiquitination

Animals

CD40 Antigens - metabolism

RNA Interference

Nedd4 Ubiquitin Protein Ligases

Mice

Oncogene Protein v-akt - metabolism

Real-Time Polymerase Chain Reaction

Details

Title: Subtitle: NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation
Creators: Di-Feng Fang - 1] State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Kun He - 1] State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Na Wang - 1] State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Zhi-Hong Sang - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Xin Qiu - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Guang Xu - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Zhao Jian - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Bing Liang - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Tao Li - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Hui-Yan Li - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Ai-Ling Li - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Tao Zhou - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Wei-Li Gong - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Baoli Yang - Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
Michael Karin - Laboratory of Gene Regulation and Signal Transduction, Cancer Center, Departments of Pharmacology and Pathology, University of California, San Diego, California 93093, USA
Xue-Min Zhang - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Wei-Hua Li - State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China
Resource Type: Journal article
Publication Details: Nature communications, Vol.5(1), pp.4513-4513
DOI: 10.1038/ncomms5513
PMID: 25072696
ISSN: 2041-1723
eISSN: 2041-1723
Language: English
Date published: 07/29/2014
Academic Unit: BioVentures Center
Record Identifier: 9984083213202771

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