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Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1–TNFR2 cooperation

Oncogene volume 28, pages 1769–1781 (2009)Cite this article

A Corrigendum to this article was published on 20 August 2009

Abstract

It has been shown that tumor necrosis factor receptor-2 (TNFR2) stimulation leads to degradation of TNF receptor associated factor-2 (TRAF2) and inhibition of TNFR1-induced activation of NFκB and JNK. Here, we show that TRAF1 inhibits TNFR2-induced proteasomal degradation of TRAF2 and relieves TNFR1-induced activation of NFκB from the inhibitory effect of TNFR2. TRAF1 co-recruited with TRAF2 to both TNF receptors. Despite lacking an amino-terminal RING/zinc-finger domain, TRAF1 did not interfere with TNFR1-induced activation of JNK and NFκB. It is noted that physiological expression levels of TRAF1 enhanced NFκB activation and interleukin-8 (IL8) production induced by TNFR2. Thus, TRAF1 shifts the quality of integrated TNFR1–TNFR2 signaling from apoptosis induction to proinflammatory NFκB signaling.

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Abbreviations

RIP:

receptor-interacting protein

IL8:

interleukin-8

MEF:

murine embryonal fibroblasts

NFκB:

nuclear factor κB

TNF:

tumor necrosis factor

TNFR1/2:

TNF receptor-1/2

TRAF1/2:

TNF receptor-associated factor-1/2

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Acknowledgements

The project was supported by Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 487, project B7, HE 5275/2-1 and Wa1025/8-1), IZKF Würzburg (project A-49) and Weyth Biopharma (Forschungspreis Rheumatologie 2007).

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Authors and Affiliations

  1. Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany

    A Wicovsky, F Henkler, S Salzmann, C Kneitz & H Wajant

  2. Institute of Cell Biology and Immunology, University Stuttgart, Stuttgart, Germany

    P Scheurich

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  1. A Wicovsky
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Correspondence to H Wajant.

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Wicovsky, A., Henkler, F., Salzmann, S. et al. Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1–TNFR2 cooperation. Oncogene 28, 1769–1781 (2009). https://doi.org/10.1038/onc.2009.29

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