J Biol Chem. 2001 Jul 27;276(30):28309-13. Epub 2001 Jun 4.

Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1.External

Poyet, J. L., Srinivasula, S. M., Tnani, M., Razmara, M., Fernandes-Alnemri, T., Alnemri, E. S.,
--- - Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Procaspase-9 contains an NH2-terminal caspase-associated recruitment domain (CARD), which is essential for direct association with Apaf-1 and activation. Procaspase-1 also contains an NH2-terminal CARD domain, suggesting that its mechanism of activation, like that of procaspase-9, involves association with an Apaf-1-related molecule. Here we describe the identification of a human Apaf-1-related protein, named Ipaf that contains an NH2-terminal CARD domain, a central nucleotide-binding domain, and a COOH-terminal regulatory leucine-rich repeat domain (LRR). Ipaf associates directly and specifically with the CARD domain of procaspase-1 through CARD-CARD interaction. A constitutively active Ipaf lacking its COOH-terminal LRR domain can induce autocatalytic processing and activation of procaspase-1 and caspase-1-dependent apoptosis in transfected cells. Our results suggest that Ipaf is a specific and direct activator of procaspase-1 and could be involved in activation of caspase-1 in response to pro-inflammatory and apoptotic stimuli.
PMID: 11390368External
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
CARD CARD12 Link CARD12 GST fusion protein pull-down Not specified Full length Not specified Not specified 1-88 Not specified 11390368
CARD CARD12 Link Caspase1 GST fusion protein pull-down Not specified 1-88 Not specified Not specified Full length Not specified 11390368
(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 CARD12 Link CARD12 Co-immunoprecipitation HEK293 Not specified Full length Not specified Full length 11390368
CARD CARD12 Link CARD12 Co-immunoprecipitation HEK293 Not specified Full length Not specified 1-88 11390368
CARD CARD12 Link Caspase1 Co-immunoprecipitation HEK293 Not specified Full length Human Full length 11390368
CARD CARD12 Link Caspase1 Co-immunoprecipitation HEK293 Not specified 1-88 Human 1-94 11390368
(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 CARD12 Link Caspase1 β-galactosidase staining Pyroptosis (Inflammasome) 11390368
(Link: click this icon to show interactions only between the two corresponding DDs)