The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation

Rojo A. Ratsimandresy, Lan H. Chu, Sonal Khare, Lucia de Almeida, Anu Gangopadhyay, Mohanalaxmi Indramohan, Alexander V. Misharin, David R. Greaves, Harris Perlman, Andrea Dorfleutner () and Christian Stehlik ()
Additional contact information
Rojo A. Ratsimandresy: Feinberg School of Medicine, Northwestern University
Lan H. Chu: Feinberg School of Medicine, Northwestern University
Sonal Khare: Feinberg School of Medicine, Northwestern University
Lucia de Almeida: Feinberg School of Medicine, Northwestern University
Anu Gangopadhyay: Feinberg School of Medicine, Northwestern University
Mohanalaxmi Indramohan: Feinberg School of Medicine, Northwestern University
Alexander V. Misharin: Feinberg School of Medicine, Northwestern University
David R. Greaves: Sir William Dunn School of Pathology, University of Oxford
Harris Perlman: Feinberg School of Medicine, Northwestern University
Andrea Dorfleutner: Feinberg School of Medicine, Northwestern University
Christian Stehlik: Feinberg School of Medicine, Northwestern University

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract Inflammasomes are protein platforms linking recognition of microbe, pathogen-associated and damage-associated molecular patterns by cytosolic sensory proteins to caspase-1 activation. Caspase-1 promotes pyroptotic cell death and the maturation and secretion of interleukin (IL)-1β and IL-18, which trigger inflammatory responses to clear infections and initiate wound-healing; however, excessive responses cause inflammatory disease. Inflammasome assembly requires the PYRIN domain (PYD)-containing adaptor ASC, and depends on PYD–PYD interactions. Here we show that the PYD-only protein POP2 inhibits inflammasome assembly by binding to ASC and interfering with the recruitment of ASC to upstream sensors, which prevents caspase-1 activation and cytokine release. POP2 also impairs macrophage priming by inhibiting the activation of non-canonical IκB kinase ɛ and IκBα, and consequently protects from excessive inflammation and acute shock in vivo. Our findings advance our understanding of the complex regulatory mechanisms that maintain a balanced inflammatory response and highlight important differences between individual POP members.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15556 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15556

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15556

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().