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Chunk #33 — Discussion

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Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC.
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Notably, ZBTB16 with UBC9 and the best characterised nuclear SUMO E3 ligase PML are all SUMO substrates7,31,32. SUMOylation appears to facilitate the formation of membrane-less organelles by phase separation which promotes protein interactions. Phase separation appears as a particular function of PML nuclear bodies in which ZBTB16 localises. Other constituents of the inflammasome such as NLRP3 and cytoskeletal proteins required to assemble inflammasomes in the cytosol are also SUMO1 substrates30,44,45. Moreover, cytoskeletal motor proteins such as dynamins, which control inflammasome activity, have been shown to bind SUMO1 and so may act to concentrate SUMOylated proteins46. Therefore SUMOylation may promote the colocation of inflammasome constituents.