RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation - CNRS - Centre national de la recherche scientifique Access content directly
Journal Articles Nature Cell Biology Year : 2008

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

Michael H Tatham
  • Function : Author
Marie-Claude Geoffroy
Linnan Shen
  • Function : Author
Anna Plechanovova
  • Function : Author
Neil Hattersley
  • Function : Author
Ellis G Jaffray
  • Function : Author
Jorma J Palvimo
  • Function : Author

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.
Fichier principal
Vignette du fichier
Tatham-Geoffroy 2008 ncb.pdf (1.1 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03082499 , version 1 (16-03-2021)

Identifiers

Cite

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, 2008, 10, pp.538 - 546. ⟨10.1038/ncb1716⟩. ⟨hal-03082499⟩

Collections

CNRS
10 View
205 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More