Biochem Biophys Res Commun. 2003 Mar 14;302(3):575-80.

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

Dowds, T. A., Masumoto, J., Chen, F. F., Ogura, Y., Inohara, N., Nunez, G.,
--- - Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
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.
PMID: 12615073External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
PYD ASC Link NLRP3 Co-immunoprecipitation HEK293 Human Not specified Human 1-96 12615073
PYD ASC Link Pyrin Co-immunoprecipitation HEK293 Human Not specified Not specified Full length 12615073
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
PYD ASC Link NLRP3 Luciferase assay NF-kB activation (Inflammasome) 12615073
PYD ASC Link Pyrin β-galactosidase staining, Luciferase assay Apoptosis inhibition NLRP3-ASC mediated NF-kB activation block 12615073
(Link: click this icon to show interactions only between the two corresponding DDs)