Infect Immun. 2007 Mar;75(3):1484-92. Epub 2006 Dec 18.

Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation.External

Dorfleutner, A., Bryan, N. B., Talbott, S. J., Funya, K. N., Rellick, S. L., Reed, J. C., Shi, X., Rojanasakul, Y., Flynn, D. C., Stehlik, C.,
--- - Mary Babb Randolph Cancer Center and Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, 2826 MBRCC, 1 Medical Center Drive, Morgantown, WV 26506-9300, USA.
Pyrin domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity against intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors, known as PYD-Nod-like receptors (NLR), PAN, PYPAF, NALP, Nod, and Caterpiller proteins, to the activation of downstream effectors, including activation of caspase-1 and NF-kappaB. Activation of these effectors occurs when specific protein complexes, known as inflammasomes, are formed. PYD signal transduction leads to inflammasome assembly and activation of specific effector proteins. It is modulated by a cellular PYD-only protein (cPOP1), which binds to ASC and interferes with the recruitment of ASC to activated PYD-NLRs. Here we describe the identification and characterization of a second cellular POP (cPOP2), which shows highest homology to the PYD of PAN1. cPOP2 binds to ASC and PAN1, thereby blocking formation of cryopyrin and PAN1-containing inflammasomes, activation of caspase-1, and subsequent processing and secretion of bioactive interleukin-1beta. Existence of a second cPOP provides additional insights into inflammasome formation and suggests that POPs might be a common regulatory mechanism to "fine-tune" the activity of specific PYD-NLR family protein-containing inflammasomes.
PMID: 17178784External
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 POP2 GST fusion protein pull-down Human Not specified In vitro translation Not specified Human E.coli 17178784
PYD ASC Link POP2 GST fusion protein pull-down Not specified Human In vitro translation Human Not specified E.coli 17178784
PYD ASC Link POP2 Yeast two-hybrid Human Not specified Yeast Human Not specified Yeast 17178784
PYD NLRP1 Link POP2 Yeast two-hybrid Not specified Not specified Yeast Human Not specified Yeast 17178784
PYD NLRP2 Link POP2 GST fusion protein pull-down Not specified Not specified In vitro translation Not specified Human E.coli 17178784
PYD NLRP2 Link POP2 GST fusion protein pull-down Not specified Not specified In vitro translation Human Not specified E.coli 17178784
PYD NLRP2 Link POP2 Yeast two-hybrid Not specified Not specified Yeast Human Not specified Yeast 17178784
(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 POP1 Co-immunoprecipitation HEK293 Human Not specified Human Not specified 17178784
PYD ASC Link POP2 Co-Immunofluorescence staining HEK293 Human Not specified Human Not specified 17178784
PYD ASC Link POP2 Co-immunoprecipitation HEK293 Human Not specified Human Not specified 17178784
PYD NLRP2 Link POP2 Co-Immunofluorescence staining HEK293 Not specified Not specified Human Not specified 17178784
PYD NLRP2 Link POP2 Co-immunoprecipitation HEK293 Not specified Not specified Human Not specified 17178784
PYD NLRP2 Link POP2 Co-immunoprecipitation HEK293 Not specified Not specified Not used Not specified 17178784
(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 POP2 ELISA IL-1b secretion decrease 17178784
PYD NLRP2 Link POP2 ELISA IL-1b secretion decrease 17178784
(Link: click this icon to show interactions only between the two corresponding DDs)