RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
| Autor: | Neil Hattersley, Anna Plechanovová, Jorma J. Palvimo, Marie-Claude Geoffroy, Ellis Jaffray, Michael H. Tatham, Ronald T. Hay, Linnan Shen |
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| Přispěvatelé: | Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee |
| Rok vydání: | 2008 |
| Předmět: |
0303 health sciences
biology [SDV]Life Sciences [q-bio] SENP6 SUMO enzymes SUMO binding macromolecular substances Cell Biology SUMO2 environment and public health Molecular biology Ubiquitin ligase Cell biology 03 medical and health sciences Promyelocytic leukemia protein 0302 clinical medicine Ubiquitin Retinoic acid receptor alpha 030220 oncology & carcinogenesis biology.protein 030304 developmental biology |
| Zdroj: | Nature Cell Biology Nature Cell Biology, Nature Publishing Group, 2008, 10, pp.538-546. ⟨10.1038/ncb1716⟩ |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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