J Biol Chem. 2002 Aug 16;277(33):29874-80. Epub 2002 May 17.

PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing.External

Wang, L., Manji, G. A., Grenier, J. M., Al-Garawi, A., Merriam, S., Lora, J. M., Geddes, B. J., Briskin, M., DiStefano, P. S., Bertin, J.,
--- - Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
PYRIN-containing Apaf1-like proteins (PYPAFs) are members of the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signal transduction proteins. We report here that PYPAF7 is a novel PYPAF protein that activates inflammatory signaling pathways. The expression of PYPAF7 is highly restricted to immune cells, and its gene maps to chromosome 19q13.4, a locus that contains a cluster of genes encoding numerous PYPAF family members. Co-expression of PYPAF7 with ASC results in the recruitment of PYPAF7 to distinct cytoplasmic loci and a potent synergistic activation of NF-kappa B. To identify other proteins involved in PYPAF7 and ASC signaling pathways, we performed a mammalian two-hybrid screen and identified pro-caspase-1 as a binding partner of ASC. Co-expression of PYPAF7 and ASC results in the synergistic activation of caspase-1 and a corresponding increase in secretion of interleukin-1 beta. In addition, PYPAF1 induces caspase-1-dependent cytokine processing when co-expressed with ASC. These findings indicate that PYPAF family members participate in inflammatory signaling by regulating the activation of NF-kappa B and cytokine processing.
PMID: 12019269External
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 Not specified 92-195 Not specified Not specified 12019269
PYD ASC Link NLRP12 Co-Immunofluorescence staining HEK293 Not specified Not specified Not specified Full length 12019269
(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-1b secretion (Inflammasome) 12019269
PYD ASC Link NLRP12 Luciferase assay, ELISA NF-kB activation, IL-1b secretion 12019269
(Link: click this icon to show interactions only between the two corresponding DDs)