SUMOylation proceeds by an enzyme cascade initiated by protease maturation by the heterodimeric SAE1/SAE2 (SUMO-activating enzyme subunit-1 and −2) E1 complex followed by covalent transfer, first to the E2 ligase UBC9 (Ubiquitin carrier protein I, also known as Ubiquitin-conjugating enzyme E2 I (UBE2I)) and subsequently to a lysine on the substrate protein13,14. The transfer of SUMO may also be shepherded by E3 substrate-recognition enzymes, although this process appears less essential than for the analogous ubiquitination. In the early 2000s, SUMO enzymes and SUMOylated proteins were found in promyelocytic leukemia (PML) bodies15,16. These subnuclear structures are assembled by the PML protein and control numerous functions, including immune defence17. Although the PML protein is an E3 SUMO enzyme and has been reported to control the cellular location of ASC7, its SUMOylation is found to be controlled by another constituent of the PML body, ZBTB16.
