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Modulation of the NF-κB pathway by virally encoded Death Effector Domains-containing proteins

Oncogene volume 18, pages 5738–5746 (1999)Cite this article

Abstract

Death Effector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex (DISC), consisting of the death domain (DD)-containing receptors and various signaling proteins. In addition, several viruses were recently shown to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs) which have the ability of blocking cell death induced by DD-containing receptors. We provide evidence that vFLIPs can also modulate the NF-κB pathway and physically interact with several signaling proteins, such as the TRAFs, RIP, NIK and the IKKs. Modulation of the NF-κB pathway may play a role in the natural history of infection by these viruses.

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Acknowledgements

We would like to thank Drs Tak Mak and Wen-Chen Yeh for FADD−/− cells, Drs Vishva Dixit, Emad Alnemri, Michael Wright, David Han, Hiroyasu Nakano, Richard Gaynor and Gioacchino Natoli for various expression plasmids, Dr Edward Clark for the NF-κB reporter plasmid, Dr Tim Rose for a DNA sample containing KSHV genome and Dr David Han for helpful discussions. PM Chaudhary was supported by a postdoctoral fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation and the Stowers Institute for Medical Research.

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Author notes

  1. Alan Jasmin and Michael T Eby: A Jasmin and MT Eby contributed equally to this work

Authors and Affiliations

  1. Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75235-8593, Texas, TX, USA

    Preet M Chaudhary, Alan Jasmin & Michael T Eby

  2. The Department of Molecular Biotechnology, University of Washington, Seattle, 98195, Washington, WA, USA

    Leroy Hood

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  1. Preet M Chaudhary
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  2. Alan Jasmin
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Chaudhary, P., Jasmin, A., Eby, M. et al. Modulation of the NF-κB pathway by virally encoded Death Effector Domains-containing proteins. Oncogene 18, 5738–5746 (1999). https://doi.org/10.1038/sj.onc.1202976

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