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Caspase-8-mediated cleavage inhibits IRF-3 protein by facilitating its proteasome-mediated degradation.

ABSTRACT: Interferon regulatory factor 3 (IRF-3) plays a central role in inducing the expression of cellular antiviral genes, including the interferon-? gene, in response to Pattern Recognition Receptors. IRF-3 is targeted for proteasome-mediated degradation, which modulates the strength and duration of the innate immune responses that depend on it. We have found that caspase-8, which is activated by cytosolic RIG-I-dependent signaling, catalyzes an essential intermediate step in the ubiquitination and proteasome-mediated degradation of IRF-3. Mutation of a consensus cleavage site within IRF-3 generates a form that is not cleaved by caspase-8 and that is protected from ubiquitination and degradation. An in vitro assay confirms the direct action of caspase-8 cleavage on IRF-3. We also show that caspase-8-mediated cleavage of IRF-3 helps to modulate dsRNA-dependent gene induction.

SUBMITTER: Sears N

PROVIDER: S-EPMC3190878 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

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Caspase-8-mediated cleavage inhibits IRF-3 protein by facilitating its proteasome-mediated degradation.

Sears Nathaniel N Sen Ganes C GC Stark George R GR Chattopadhyay Saurabh S

The Journal of biological chemistry 20110804 38

Interferon regulatory factor 3 (IRF-3) plays a central role in inducing the expression of cellular antiviral genes, including the interferon-β gene, in response to Pattern Recognition Receptors. IRF-3 is targeted for proteasome-mediated degradation, which modulates the strength and duration of the innate immune responses that depend on it. We have found that caspase-8, which is activated by cytosolic RIG-I-dependent signaling, catalyzes an essential intermediate step in the ubiquitination and pr ...[more]

PMID: 21816816

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Dataset Information

Caspase-8-mediated cleavage inhibits IRF-3 protein by facilitating its proteasome-mediated degradation.

Publications

Caspase-8-mediated cleavage inhibits IRF-3 protein by facilitating its proteasome-mediated degradation.

Similar Datasets

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