Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression of a subset of NF-κB target genes

Mol Cell. 2012 Apr 27;46(2):200-11. doi: 10.1016/j.molcel.2012.02.016. Epub 2012 Mar 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology
  • Caspase 7 / physiology*
  • Chromatin / metabolism
  • Gene Expression Regulation
  • Humans
  • Inflammation / genetics
  • Mice
  • Mutation
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / physiology*
  • Signal Transduction


  • Carrier Proteins
  • Chromatin
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspase 7