Cell Death Differ. 2006 Feb;13(2):236-49.

Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization.External

Yu, J. W., Wu, J., Zhang, Z., Datta, P., Ibrahimi, I., Taniguchi, S., Sagara, J., Fernandes-Alnemri, T., Alnemri, E. S.,
--- - Department of Microbiology and Immunology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Mutations in cryopyrin and pyrin proteins are responsible for several autoinflammatory disorders in humans, suggesting that these proteins play important roles in regulating inflammation. Using a HEK293 cell-based reconstitution system that stably expresses ASC and procaspase-1 we demonstrated that neither cryopyrin nor pyrin or their corresponding disease-associated mutants could significantly activate NF-kappaB in this system. However, both cryopyrin and two disease-associated cryopyrin mutants induced ASC oligomerization and ASC-dependent caspase-1 activation, with the disease-associated mutants being more potent than the wild-type (WT) cryopyrin, because of increased self-oligomerization. Contrary to the proposed anti-inflammatory activity of WT pyrin, our results demonstrated that pyrin, like cryopyrin, can also assemble an inflammasome complex with ASC and procaspase-1 leading to ASC oligomerization, caspase-1 activation and interleukin-1beta processing. Thus, we propose that pyrin could function as a proinflammatory molecule.
PMID: 16037825External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
PYD ASC Link Pyrin His fusion protein pull-down Human Full length HEK293 Not specified Full length Sf-9 16037825
(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
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
PYD ASC Link NLRP3 Co-Immunofluorescence staining HEK293 Human Full length Not specified Full length 16037825
PYD ASC Link Pyrin Co-immunoprecipitation HEK293 Human Full length Not specified Not specified 16037825
(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 Caspase cleaved assay Caspase1 activation (Inflammasome) 16037825
PYD ASC Link Pyrin Caspase cleaved assay Caspase1 activation (Inflammasome) 16037825
(Link: click this icon to show interactions only between the two corresponding DDs)