Group Leader

Dr. Andrea Pichler
Dr. Andrea Pichler
Group Leader
Phone:+49 761 5108-777

Lab Andrea Pichler

Laboratory Andrea Pichler

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.

Figure 1 The ZNF451 family presents a novel class of SUMO conjugating enzymes with E3 and E4 activities (upper panel). A tandem SIM and the interSIM region display the catalytic unit of the enzymes. E3 and E4 activities involve distinct substrate (acceptor) binding interfaces (lower, left panel). The ZNF451 family has four family members which share the N-terminal catalytic unit but differ in their substrate recruiting C-termini (lower, right panel).  Zoom Image
Figure 1 The ZNF451 family presents a novel class of SUMO conjugating enzymes with E3 and E4 activities (upper panel). A tandem SIM and the interSIM region display the catalytic unit of the enzymes. E3 and E4 activities involve distinct substrate (acceptor) binding interfaces (lower, left panel). The ZNF451 family has four family members which share the N-terminal catalytic unit but differ in their substrate recruiting C-termini (lower, right panel).  [less]

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).

 
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