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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product.

Cryopyrin, a member of the Nod protein family mutated in familial cold urticaria and Muckle-Wells syndrome, has been recently implicated in inflammation. However, the mechanism of activation and regulation of the cryopyrin signaling pathway remains poorly understood. We report here that co-expression of cryopyrin with its binding partner, ASC, induced both apoptosis and NF-kappaB activation. This signaling was mimicked by oligomerization of ASC, suggesting that cryopyrin activates downstream targets as reported for other Nod family members. Notably, pyrin, the product of the familial Mediterranean fever gene, inhibited cryopyrin- mediated apoptosis and NF-kappaB activation by disrupting the cryopyrin-ASC interaction. These results provide evidence for a cryopyrin signaling pathway activated through the induced proximity of ASC, which is negatively regulated by pyrin.[1]

References

  1. Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product. Dowds, T.A., Masumoto, J., Chen, F.F., Ogura, Y., Inohara, N., Núñez, G. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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