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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
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Volume 389, Issue 10 (Oct 2008)

Issues

Pursuing different ‘TRADDes’: TRADD signaling induced by TNF-receptor 1 and the Epstein-Barr virus oncoprotein LMP1

Arnd Kieser
  • 1Abteilung Genvektoren, Helmholtz Zentrum München – Deutsches Forschungszentrum für Gesundheit und Umwelt, Marchioninistrasse 25, D-81377 München, Germany
  • Other articles by this author:
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Published Online: 2008-08-19 | DOI: https://doi.org/10.1515/BC.2008.144

Abstract

The pro-apoptotic tumor necrosis factor (TNF)-receptor 1-associated death domain protein (TRADD) was initially identified as the central signaling adapter molecule of TNF-receptor 1 (TNFR1). Upon stimulation with the pro-inflammatory cytokine TNFα, TRADD is recruited to the activated TNFR1 by direct interaction between the death domains of both molecules. TRADD mediates TNFR1 activation of NF-κB and c-Jun N-terminal kinase (JNK), as well as caspase-dependent apoptosis. Surprisingly, TRADD is also recruited by latent membrane protein 1 (LMP1), the major oncoprotein of the human Epstein-Barr tumor virus. By mimicking a constitutively active receptor, LMP1 is essential for B-cell transformation by the virus, activating NF-κB, phosphatidylinositol 3-kinase, JAK/STAT and mitogen-activated protein kinase signaling. In contrast to TNFR1, LMP1's interaction with TRADD is independent of a functional death domain. The unique structure of the LMP1-TRADD complex dictates an unusual type of TRADD-dependent NF-κB signaling and subverts TRADD's potential to induce apoptosis. This article provides an overview of TNFR1 and LMP1 signal transduction with a focus on TRADD's functions in apoptotic and transforming signaling, incorporating recent results from TRADD RNAi and knockout studies.

Keywords: apoptosis; latent membrane protein 1 (LMP1); NF-κB; TNF-receptor 1; TRADD; transformation

About the article


Received: 2008-03-19

Accepted: 2008-06-05

Published Online: 2008-08-19

Published in Print: 2008-10-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2008.144.

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