Cell. 2007 Apr 6;129(1):45-56.

Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1.External

Bruey, J. M., Bruey-Sedano, N., Luciano, F., Zhai, D., Balpai, R., Xu, C., Kress, C. L., Bailly-Maitre, B., Li, X., Osterman, A., Matsuzawa, S., Terskikh, A. V., Faustin, B., Reed, J. C.,
--- - Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Caspases are intracellular proteases that cleave substrates involved in apoptosis or inflammation. In C. elegans, a paradigm for caspase regulation exists in which caspase CED-3 is activated by nucleotide-binding protein CED-4, which is suppressed by Bcl-2-family protein CED-9. We have identified a mammalian analog of this caspase-regulatory system in the NLR-family protein NALP1, a nucleotide-dependent activator of cytokine-processing protease caspase-1, which responds to bacterial ligand muramyl-dipeptide (MDP). Antiapoptotic proteins Bcl-2 and Bcl-X(L) bind and suppress NALP1, reducing caspase-1 activation and interleukin-1beta (IL-1beta) production. When exposed to MDP, Bcl-2-deficient macrophages exhibit more caspase-1 processing and IL-1beta production, whereas Bcl-2-overexpressing macrophages demonstrate less caspase-1 processing and IL-1beta production. The findings reveal an interaction of host defense and apoptosis machinery.
PMID: 17418785External
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 Apaf1 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 17418785
CARD CARD12 Link Caspase1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 17418785
CARD Caspase1 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 17418785
CARD Caspase5 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 17418785
PYD ASC Link NLRP1 Co-immunoprecipitation THP-1 17418785
PYD ASC Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 17418785
(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 Caspase1 Link NLRP1 ELISA IL-1b secretion increase 17418785
CARD Caspase5 Link NLRP1 ELISA IL-1b secretion increase 17418785
(Link: click this icon to show interactions only between the two corresponding DDs)