J Biol Chem. 2002 Mar 29;277(13):11570-5. Epub 2002 Jan 10.

PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B.External

Manji, G. A., Wang, L., Geddes, B. J., Brown, M., Merriam, S., Al-Garawi, A., Mak, S., Lora, J. M., Briskin, M., Jurman, M., Cao, J., DiStefano, P. S., Bertin, J.,
--- - Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
The PYRIN domain is a recently identified protein-protein interaction domain that is found at the N terminus of several proteins thought to function in apoptotic and inflammatory signaling pathways. We report here that PYPAF1 (PYRIN-containing Apaf1-like protein 1) is a novel PYRIN-containing signaling protein that belongs to the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signaling proteins. The expression of PYPAF1 is highly restricted to immune cells, and its gene maps to chromosome 1q44, a locus that is associated with the rare inflammatory diseases Muckle-Wells syndrome and familial cold urticaria. To identify downstream signaling partners of PYPAF1, we performed a mammalian two-hybrid screen and identified ASC as a PYRIN-containing protein that interacts selectively with the PYRIN domain of PYPAF1. When expressed in cells, ASC recruits PYPAF1 to distinct cytoplasmic loci and induces the activation of NF-kappaB. Furthermore, coexpression of PYPAF1 with ASC results in a potent synergistic activation of NF-kappaB. These findings suggest that PYPAF1 and ASC function as upstream activators of NF-kappaB signaling.
PMID: 11786556External
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
PYD ASC Link NLRP3 Two-hybrid Not specified 1-110 HEK293 Not specified 1-116 HEK293 11786556
(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
PYD ASC Link NLRP3 Co-Immunofluorescence staining HEK293 Not specified Not specified Not specified Full length 11786556
PYD ASC Link NLRP3 Co-Immunofluorescence staining HEK293 Not specified Not specified Not specified 1-739 11786556
(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
PYD ASC Link NLRP3 Luciferase assay NF-kB activation (Inflammasome) 11786556
(Link: click this icon to show interactions only between the two corresponding DDs)