%0 Journal Article %T RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation %+ Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences %A Tatham, Michael, H %A Geoffroy, Marie-Claude %A Shen, Linnan %A Plechanovova, Anna %A Hattersley, Neil %A Jaffray, Ellis, G %A Palvimo, Jorma, J %A Hay, Ronald, T %< avec comité de lecture %@ 1465-7392 %J Nature Cell Biology %I Nature Publishing Group %V 10 %P 538 - 546 %8 2008-04-13 %D 2008 %R 10.1038/ncb1716 %Z Life Sciences [q-bio]Journal articles %X 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. %G English %2 https://cnrs.hal.science/hal-03082499/document %2 https://cnrs.hal.science/hal-03082499/file/Tatham-Geoffroy%202008%20ncb.pdf %L hal-03082499 %U https://cnrs.hal.science/hal-03082499 %~ CNRS