title: Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression of a subset of NF-κB target genes.
abstract: Caspase 1 is part of the inflammasome, which is assembled upon pathogen recognition, while caspases 3 and/or 7 are mediators of apoptotic and nonapoptotic functions. PARP1 cleavage is a hallmark of apoptosis yet not essential, suggesting it has another physiological role. Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, translocates to the nucleus, and cleaves PARP1 at the promoters of a subset of NF-κB target genes negatively regulated by PARP1. Mutating the PARP1 cleavage site D214 renders PARP1 uncleavable and inhibits PARP1 release from chromatin and chromatin decondensation, thereby restraining the expression of cleavage-dependent NF-κB target genes. These findings propose an apoptosis-independent regulatory role for caspase 7-mediated PARP1 cleavage in proinflammatory gene expression and provide insight into inflammasome signaling.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Süheda
authors.initials: S
authors.lastname: Erener
authors.forename: Virginie
authors.initials: V
authors.lastname: Pétrilli
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kassner
authors.forename: Roberta
authors.initials: R
authors.lastname: Minotti
authors.forename: Rosa
authors.initials: R
authors.lastname: Castillo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santoro
authors.forename: Paul O
authors.initials: PO
authors.lastname: Hassa
authors.forename: Jürg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053179:Caspase 7 / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053179:Caspase 7