Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein latent membrane protein 1

Ping Xie; Gail A Bishop

doi:10.4049/jimmunol.173.9.5546

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Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein latent membrane protein 1

Journal article

Peer reviewed

Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein latent membrane protein 1

Ping Xie and Gail A Bishop

The Journal of immunology (1950), Vol.173(9), pp.5546-5555

11/01/2004

DOI: 10.4049/jimmunol.173.9.5546

PMID: 15494504

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Abstract

TNFR-associated factor (TRAF)3, an adaptor protein that binds the cytoplasmic domains of both CD40 and the EBV-encoded oncoprotein latent membrane protein (LMP)1, is required for positive signaling by LMP1 but not CD40 in B lymphocytes. The present study further investigated how TRAF3 participates in LMP1 signaling. We found that TRAF3 mediates signaling both through direct interactions with the C-terminal activating region (CTAR)1 of LMP1 and through indirect interactions with the CTAR2 region of LMP1 in mouse B cells. Notably, our results demonstrated that the CTAR2 region appears to inhibit the recruitment of TRAF1 and TRAF2 to membrane rafts by the CTAR1 region. Additionally, the absence of TRAF2 in B cells resulted in only a modest reduction in CTAR1-mediated signals and no detectable effect on CTAR2-mediated signals. CTAR1 and CTAR2 cooperated to achieve the robust signaling activity of LMP1 when recruited to the same membrane microdomains in B cells. Interestingly, TRAF3 deficiency completely abrogated the cooperation between CTAR1 and CTAR2, supporting the hypothesis that TRAF3 participates in the physical interaction between CTAR1 and CTAR2 of LMP1. Together, our findings highlight the central importance of TRAF3 in LMP1-mediated signaling, which is critical for EBV persistent infection and EBV-associated pathogenesis.

Protein Binding - genetics

TNF Receptor-Associated Factor 3 - physiology

Cytoplasm - metabolism

TNF Receptor-Associated Factor 2 - physiology

Viral Matrix Proteins - physiology

Receptors, Tumor Necrosis Factor - physiology

Peptide Fragments - physiology

Signal Transduction - immunology

Transfection

TNF Receptor-Associated Factor 3 - genetics

B-Lymphocytes - virology

Viral Matrix Proteins - metabolism

Peptide Fragments - genetics

B-Lymphocytes - metabolism

Oncogene Proteins, Viral - metabolism

Oncogene Proteins, Viral - physiology

Cell Line

Peptide Fragments - metabolism

Epstein-Barr Virus Infections - immunology

TNF Receptor-Associated Factor 3 - metabolism

Protein Structure, Tertiary - genetics

Signal Transduction - genetics

Animals

Mice

Mutation

Amino Acid Motifs - genetics

Epstein-Barr Virus Infections - metabolism

Details

Title: Subtitle: Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein latent membrane protein 1
Creators: Ping Xie - Department of Microbiology, University of Iowa, Iowa City, IA 52242 , USA
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.173(9), pp.5546-5555
DOI: 10.4049/jimmunol.173.9.5546
PMID: 15494504
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI49993 / NIAID NIH HHS AI28847 / NIAID NIH HHS CA099997 / NCI NIH HHS
Language: English
Date published: 11/01/2004
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984002377102771

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