The ZNF451 family, a novel class of SUMO enzymes
Very recently, we discovered a novel family of SUMO conjugating enzymes with E3 ligase and E4 elongase (specialized E3s for SUMO chain elongation) functions (Figure 1, upper panel). We show that ZNF451, a mainly uncharacterized zinc finger protein, has SUMO E3 ligase activity and efficiently assembles SUMO2/3 chains. Detailed biochemical analysis demonstrates that ZNF451 functions distinct to all known E3 ligases described for SUMO and ubiquitin conjugation: ZNF451 executes catalysis via a tandem-SIM and its interSIM region.
One SIM orients the donor-SUMO, while a second SIM binds SUMO on the backside of the E2 enzyme. Intriguingly, this short tandem-SIM region is sufficient to extend a backside-anchored SUMO chain (E4 elongase activity) in contrast to chain initiation, which in addition requires a zinc finger region to recruit the initial acceptor SUMO (E3 ligase activity, Figure 1, lower left panel). Four human proteins share this E4-elongase activity (Figure 1, lower right panel) and are involved in stress-induced global sumo(2,3)ylation after DNA double strand break induction or proteasome inhibition in vivo (Eisenhardt, Chaugule et al 2015 and Cappadocia et al 2015).