TRAF3 as a powerful and multitalented regulator of lymphocyte functions

Gail A Bishop

doi:10.1189/jlb.2MR0216-063R

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TRAF3 as a powerful and multitalented regulator of lymphocyte functions

Journal article

Open access

Peer reviewed

TRAF3 as a powerful and multitalented regulator of lymphocyte functions

Gail A Bishop

Journal of leukocyte biology, Vol.100(5), pp.919-926

11/2016

DOI: 10.1189/jlb.2MR0216-063R

PMCID: PMC6608063

PMID: 27154354

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Abstract

This review summarizes the current state of knowledge regarding the roles of the signaling adapter protein tumor necrosis factor receptor (TNFR)-associated factor 3 in regulating the functions of B and T lymphocytes. In B lymphocytes, TNFR-associated factor 3 inhibits signaling by TNFR superfamily receptors, Toll-like receptors, and interleukin-6R. In contrast, signaling to B cells by the virally encoded oncogenic protein latent membrane protein 1 is promoted by TNFR-associated factor 3. An important B cell-specific role for TNFR-associated factor 3 is the inhibition of homeostatic survival, directly relevant to the common occurrence of TNFR-associated factor 3 mutations in human B cell malignancies. TNFR-associated factor 3 was recently found to be a resident nuclear protein in B cells, where it interacts with and inhibits gene expression mediated by the cAMP response element-binding protein transcription complex, including expression of the prosurvival protein myeloid leukemia cell differentiation protein 1. In T lymphocytes, TNFR-associated factor 3 is required for normal signaling by the T cell antigen receptor, while inhibiting signaling by the interleukin-2 receptor. Cytoplasmic TNFR -associated factor 3 restrains nuclear factor-κB2 activation in both T and B cells. Clinical implications and future directions for the study of this context-dependent signaling regulator are discussed.

Cell Line

TNF Receptor-Associated Factor 3 - deficiency

Cell Survival

Humans

NF-kappa B - metabolism

Immunity, Innate

Nuclear Proteins - immunology

Protein Kinase C-delta - immunology

Forecasting

Lymphocyte Subsets - immunology

Mice, Knockout

Animals

B-Lymphocytes - immunology

TNF Receptor-Associated Factor 3 - immunology

Antibody Formation

Receptors, Cytokine - immunology

T-Lymphocytes - immunology

Mice

Viral Matrix Proteins - immunology

Receptor-CD3 Complex, Antigen, T-Cell - immunology

CD40 Antigens - immunology

Details

Title: Subtitle: TRAF3 as a powerful and multitalented regulator of lymphocyte functions
Creators: Gail A Bishop - Department of Veterans Affairs Medical Center, Iowa City, Iowa, USA gail-bishop@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.100(5), pp.919-926
Publisher: United States
DOI: 10.1189/jlb.2MR0216-063R
PMID: 27154354
PMCID: PMC6608063
ISSN: 0741-5400
eISSN: 1938-3673
Grant note: P30 ES005605 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
Language: English
Date published: 11/2016
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001209302771

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