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Title

The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases
Authors
Rebsamen, Manuele
Meylan, Etienne
Curran, Joseph
Tschopp, Jean-Marie
Published in Cell Death and Differentiation. 2008, vol. 15, no. 11, p. 1804-11
Abstract The outcome of a viral infection depends on the interplay between the host's capacity to trigger potent antiviral responses and viral mechanisms that counteract them. Although Toll-like receptor (TLR)-3, which recognizes virally derived double-stranded (ds) RNA, transmits downstream antiviral signaling through the TIR adaptor Trif (TICAM-1), viral RNA-sensing RIG-like helicases (RLHs) use the mitochondrial-bound CARD protein Cardif (IPS-1/MAVS/VISA). The importance of these two antiviral signaling pathways is reflected by the fact that both adaptors are inhibited through specific cleavage triggered by the hepatitis C virus serine protease NS3-4A. Here, we show that inactivation can also occur through cellular caspases activated by various pro-apoptotic signals. Upon caspase-dependent cleavage both adaptors loose their capacity to activate the transcription factors interferon regulatory factors (IRF) and NF-kappaB. Importantly, poliovirus infection triggers a caspase-dependent cleavage of Cardif, suggesting that some viruses may activate caspases not only as a mean to facilitate shedding and replication, but also to impair antiviral responses.
Keywords Adaptor Proteins, Signal Transducing/metabolism — Adaptor Proteins, Vesicular Transport/metabolism — Antiviral Agents/metabolism — Caspases/metabolism — Hela Cells — Humans — Interferon Regulatory Factors/metabolism — Models, Biological — Poliovirus/physiology — Protein Processing, Post-Translational
Identifiers
PMID: 18756281
Full text
Article (Accepted version) (221 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www.nature.com/cdd/journal/v15/n11/full/cdd2008119a.html
Structures
Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research group Régulation traductionnelle dans les cellules de mammifère (631)
Citation
(ISO format) 		REBSAMEN, Manuele et al. The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases. In: Cell Death and Differentiation, 2008, vol. 15, n° 11, p. 1804-11. doi: 10.1038/cdd.2008.119 https://archive-ouverte.unige.ch/unige:1889

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Deposited on : 2009-06-04

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