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RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation

Abstract : In acute promyelocytic leukaemia (APL), promyelocytic leukaemia (PML) protein is fused to the retinoic acid receptor α (RAR). This disease can be treated effectively with arsenic, which induces PML modification by small ubiquitin-like modifiers (SUMO) and proteasomal degradation. Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. In RNF4-depleted cells, PML protein accumulated and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro. In the absence of RNF4, arsenic failed to induce degradation of PML and SUMO-modified PML accumulated in the nucleus. These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis.
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Contributor : Marie-Claude Geoffroy Connect in order to contact the contributor
Submitted on : Tuesday, March 16, 2021 - 10:59:43 AM
Last modification on : Tuesday, March 16, 2021 - 3:18:26 PM
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Michael H Tatham, Marie-Claude Geoffroy, Linnan Shen, Anna Plechanovova, Neil Hattersley, et al.. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nature Cell Biology, Nature Publishing Group, 2008, 10, pp.538 - 546. ⟨10.1038/ncb1716⟩. ⟨hal-03082499⟩



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