Regulation of TRAF2 signaling by self-induced degradation

Kevin D Brown; Bruce S Hostager; Gail A Bishop

doi:10.1074/jbc.m111522200

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Regulation of TRAF2 signaling by self-induced degradation

Journal article

Open access

Peer reviewed

Regulation of TRAF2 signaling by self-induced degradation

Kevin D Brown, Bruce S Hostager and Gail A Bishop

The Journal of biological chemistry, Vol.277(22), pp.19433-19438

05/31/2002

DOI: 10.1074/jbc.m111522200

PMID: 11909853

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Abstract

Receptors belonging to the tumor necrosis factor receptor (TNF-R) family utilize cytoplasmic adapter proteins called TNF-R-associated factors (TRAFs) as key elements in their signaling pathways. However, it is not yet clear how individual TRAFs regulate signaling by this large and growing receptor family. Signaling via the TNF-R family member CD40 has recently been shown to result in recruitment of TRAF2 to plasma membrane detergent-resistant microdomains (lipid rafts) as well as to subsequently initiate TRAF2 degradation. As TRAF2 associates with most members of the TNF-R family, we wished to determine how this degradation occurs. We show here that CD40-mediated TRAF2 degradation requires the zinc-binding RING domain of TRAF2 and is preceded by TRAF2 ubiquitination, suggesting that the TRAF2 RING may promote ubiquitination although the RING itself is not a target of ubiquitination. Several approaches show that ubiquitination and proteasomal activity are integral to TRAF2 degradation, and inhibition of this process potentiates CD40 signaling.

Transfection

Signal Transduction

Membrane Microdomains - metabolism

Zinc - metabolism

Insecta

Ubiquitin - metabolism

Proteasome Endopeptidase Complex

TNF Receptor-Associated Factor 2

CD40 Antigens - metabolism

JNK Mitogen-Activated Protein Kinases

CHO Cells

Protein Structure, Tertiary

Cell Line

Cysteine Endopeptidases

Cricetinae

DNA - metabolism

Multienzyme Complexes - antagonists & inhibitors

Plasmids - metabolism

Animals

Proteins - metabolism

Protein Binding

Mice

Proteins - chemistry

Lysine - chemistry

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: Regulation of TRAF2 signaling by self-induced degradation
Creators: Kevin D Brown - Department of Microbiology and Internal Medicine, University of Iowa College of Medicine and the Veteran's Affairs Medical Center, Iowa City, Iowa 52242, USA
Bruce S Hostager
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(22), pp.19433-19438
DOI: 10.1074/jbc.m111522200
PMID: 11909853
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: AI28847 / NIAID NIH HHS CA66570 / NCI NIH HHS DK25295 / NIDDK NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 05/31/2002
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001216802771

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