Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Molecular Biology of the Cell Année : 2010

Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies

Résumé

In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML.
Fichier principal
Vignette du fichier
Geoffroy MC 2010 RNF4-PML.pdf (2.75 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03082477 , version 1 (18-12-2020)

Identifiants

Citer

Marie-Claude Geoffroy, Ellis G Jaffray, Katherine J Walker, Ronald Thomas Hay. Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies. Molecular Biology of the Cell, 2010, ⟨10.1091/mbc.E10⟩. ⟨hal-03082477⟩

Collections

CNRS
12 Consultations
30 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More