J Biol Chem. 2002 Jun 14;277(24):21119-22. Epub 2002 Apr 19.

The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.External

Srinivasula, S. M., Poyet, J. L., Razmara, M., Datta, P., Zhang, Z., Alnemri, E. S.,
--- - Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
The PYRIN and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the apoptotic and inflammatory signaling pathways. Here we show that the PYRIN-CARD protein ASC functions as a caspase-1-activating adaptor. ASC interacted specifically with procaspase-1 via CARD-CARD interactions and induced its oligomerization. Consistent with these results ectopic expression of full-length ASC, but not its isolated CARD or PYRIN domain, with procaspase-1 induced activation of procaspase-1 and processing of pro-interleukin-1beta in transfected cells. Substitution of the PYRIN domain of ASC with an inducible FKBP12 oligomerization domain produced a molecule that can induce caspase-1 activation in response to stimulation with the oligomerization drug AP20187, suggesting that the PYRIN domain functions as an oligomerization domain, whereas the CARD domain functions as the effector domain in the caspase-1 activation pathway. Furthermore stable expression of an isolated CARD of ASC in THP-1 cells diminished interleukin-1beta generation in response to pro-inflammatory cytokines. These results indicate that ASC is involved in the caspase-1 signaling pathway by mediating the assembly of a caspase-1-inflammasome signaling complex in response to pro-inflammatory cytokine stimulation.
PMID: 11967258External
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 ASC Link CARD12 GST fusion protein pull-down Human 105-195 In vitro translation Human 1-88 E.coli 11967258
CARD ASC Link CARD12 GST fusion protein pull-down Human Full length In vitro translation Human 1-88 E.coli 11967258
CARD ASC Link CARD16 GST fusion protein pull-down Human 105-195 In vitro translation Human Full length E.coli 11967258
CARD ASC Link CARD16 GST fusion protein pull-down Human Full length In vitro translation Human Full length E.coli 11967258
CARD ASC Link Caspase1 GST fusion protein pull-down Human 105-195 In vitro translation Not specified Not specified E.coli 11967258
CARD ASC Link Caspase1 GST fusion protein pull-down Human Full length In vitro translation Not specified Not specified E.coli 11967258
(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 ASC Link Caspase1 Co-immunoprecipitation HEK293 Human 105-195 Not specified Not specified 11967258
CARD ASC Link Caspase1 Co-immunoprecipitation HEK293 Human Full length Not specified Not specified 11967258
(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 ASC Link Caspase1 ELISA IL-1 secretion (Inflammasome) 11967258
(Link: click this icon to show interactions only between the two corresponding DDs)