We identify the lysine residues at positions 21 and 109 on ASC control its SUMOylation. The lysine residue number 21 is part of the interface between ASC oligomerized monomers38. Accordingly, it is envisaged that conjugation of SUMO1 at this location would obstruct the formation of the ASC filament unless this was subsequently removed by a SUMO1 protease. Interestingly, it has been shown by others that disruption of protein binding at the PYD of ASC promotes inflammasome activity by increasing the recruitment of pro-Caspase-1 via the proteins’ mutual CARDs43. Conceivably, SUMOylation of ASC’s PYD might function in this way to promote inflammasome assembly.
