Immunity. 2004 Mar;20(3):319-25.

NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.External

Agostini, L., Martinon, F., Burns, K., McDermott, M. F., Hawkins, P. N., Tschopp, J.,
--- - Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Mutations within the NALP3/cryopyrin/CIAS1 gene are responsible for three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. The NALP3 protein is homologous to NALP1, which is a component of the inflammasome, a molecular platform that activates the proinflammatory caspases-1 and -5. NALP3 (and other members of the NALP family) lacks the C-terminal, CARD-containing sequence of NALP1, and its role in caspase activation is unclear. Here, we report that NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity. Macrophages from Muckle-Wells patients spontaneously secrete active IL-1beta. Increased inflammasome activity is therefore likely to be the molecular basis of the symptoms associated with NALP3-dependent autoinflammatory disorders.
PMID: 15030775External
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 ASC Co-immunoprecipitation Not specified Not specified HEK293 THP-1 lysate 15030775
PYD ASC Link NLRP2 Co-immunoprecipitation THP-1 lysate Human 1-93 HEK293 15030775
PYD ASC Link NLRP3 Co-immunoprecipitation THP-1 lysate Not specified 1-112 HEK293 15030775
(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
CARD CARD8 Link Caspase1 Co-immunoprecipitation HEK293 Not specified 320-431 Not specified Not specified 15030775
PYD ASC Link ASC Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 15030775
PYD ASC Link NLRP2 Co-immunoprecipitation HEK293 Not specified Not specified Human 1-93 15030775
PYD ASC Link NLRP2 Co-immunoprecipitation THP-1 Not used Human Full length 15030775
PYD ASC Link NLRP3 Co-immunoprecipitation HEK293 Not specified Not specified Not specified 1-112 15030775
PYD ASC Link NLRP3 Co-immunoprecipitation THP-1 15030775
PYD ASC Link NLRP3 Co-immunoprecipitation HEK293 Not specified Not specified Human 1-112 15030775
(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) 15030775
(Link: click this icon to show interactions only between the two corresponding DDs)