Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

Nat Commun. 2023 Dec 20;14(1):8465. doi: 10.1038/s41467-023-43945-1.

Abstract

Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism
  • Caspase 1 / metabolism
  • Inflammasomes* / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Protein Binding
  • Sumoylation

Substances

  • CARD Signaling Adaptor Proteins
  • Caspase 1
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Zbtb16 protein, mouse