Journal article
TRAF3 as a Multifaceted Regulator of B Lymphocyte Survival and Activation
Frontiers in immunology, Vol.9, pp.2161-2161
09/24/2018
DOI: 10.3389/fimmu.2018.02161
PMID: 30319624
Abstract
The adaptor protein TNF receptor-associated factor 3 (TRAF3) serves as a powerful negative regulator in multiple aspects of B cell biology. Early
in vitro
studies in transformed cell lines suggested the potential of TRAF3 to inhibit signaling by its first identified binding receptor, CD40. However, because the canonical TRAF3 binding site on many receptors also mediates binding of other TRAFs, and whole-mouse TRAF3 deficiency is neonatally lethal, an accurate understanding of TRAF3's specific functions was delayed until conditional TRAF3-deficient mice were produced. Studies of B cell-specific TRAF3-deficient mice, complemented by investigations in normal and malignant mouse and human B cells, reveal that TRAF3 has powerful regulatory roles that are unique to this TRAF, as well as functions context-specific to the B cell. This review summarizes the current state of knowledge of these roles and functions. These include inhibition of signaling by plasma membrane receptors, negative regulation of intracellular receptors, and restraint of cytoplasmic NF- κB pathways. TRAF3 is also now known to function as a resident nuclear protein, and to impact B cell metabolism. Through these and additional mechanisms TRAF3 exerts powerful restraint upon B cell survival and activation. It is thus perhaps not surprising that TRAF3 has been revealed as an important tumor suppressor in B cells. The many and varied functions of TRAF3 in B cells, and new directions to pursue in future studies, are summarized and discussed here.
Details
- Title: Subtitle
- TRAF3 as a Multifaceted Regulator of B Lymphocyte Survival and Activation
- Creators
- Gail A Bishop - ,Laura L Stunz - ,Bruce S Hostager - ,
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.9, pp.2161-2161
- DOI
- 10.3389/fimmu.2018.02161
- PMID
- 30319624
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 09/24/2018
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001210002771
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