Immunity. 2004 Mar;20(3):319-25.
NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.
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.
--- - 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: 15030775

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In vitro interaction | |||||||||||||
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DD1 | DD2 | Reference | |||||||||||
Family | DD1 | DD2 | Method | Species | Region | Expression | Species | Region | Expression | ||||
PYD | ASC |
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ASC | Co-immunoprecipitation | Not specified | Not specified | HEK293 | THP-1 lysate | 15030775 | ||||
PYD | ASC |
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NLRP2 | Co-immunoprecipitation | THP-1 lysate | Human | 1-93 | HEK293 | 15030775 | ||||
PYD | ASC |
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NLRP3 | Co-immunoprecipitation | THP-1 lysate | Not specified | 1-112 | HEK293 | 15030775 |
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: click this icon to show interactions only between the two corresponding DDs)

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In vivo interaction | |||||||||||||
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Endogenous expression |
Overexpression | DD1 | DD2 | Reference | |||||||||
Family | DD1 | DD2 | Method | Species | Region | Species | Region | ||||||
CARD | CARD8 |
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Caspase1 | Co-immunoprecipitation | HEK293 | Not specified | 320-431 | Not specified | Not specified | 15030775 | |||
PYD | ASC |
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ASC | Co-immunoprecipitation | HEK293 | Not specified | Not specified | Not specified | Not specified | 15030775 | |||
PYD | ASC |
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NLRP2 | Co-immunoprecipitation | HEK293 | Not specified | Not specified | Human | 1-93 | 15030775 | |||
PYD | ASC |
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NLRP2 | Co-immunoprecipitation | THP-1 | Not used | Human | Full length | 15030775 | ||||
PYD | ASC |
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NLRP3 | Co-immunoprecipitation | HEK293 | Not specified | Not specified | Not specified | 1-112 | 15030775 | |||
PYD | ASC |
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NLRP3 | Co-immunoprecipitation | THP-1 | 15030775 | |||||||
PYD | ASC |
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NLRP3 | Co-immunoprecipitation | HEK293 | Not specified | Not specified | Human | 1-112 | 15030775 |
(
: click this icon to show interactions only between the two corresponding DDs)

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Functional Role | |||||||||||
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Family | DD1 | DD2 | Method | Death-related | Death-unrelated | Reference | |||||
PYD | ASC |
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NLRP3 | Caspase cleaved assay | Caspase1 activation (Inflammasome) | 15030775 |
(
: click this icon to show interactions only between the two corresponding DDs)
