Mol Cell. 2002 Aug;10(2):417-26.

The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.External

Martinon, F., Burns, K., Tschopp, J.,
--- - Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of Pycard. Moreover, expression of a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
PMID: 12191486External
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
CARD ASC Link caspase1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12191486
CARD Caspase2 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12191486
CARD Caspase4 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12191486
CARD Caspase5 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12191486
(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
CARD Caspase5 Link NLRP1 Caspase cleaved assay Caspase5 activation (Inflammasome) 12191486
(Link: click this icon to show interactions only between the two corresponding DDs)