RESUMEN
RNF4 (RING finger protein 4) is a STUbL [SUMO (small ubiquitin-related modifier)-targeted ubiquitin ligase] controlling PML (promyelocytic leukaemia) nuclear bodies, DNA double strand break repair and other nuclear functions. In the present paper, we describe that the sequence and spacing of the SIMs (SUMO-interaction motifs) in RNF4 regulate the avidity-driven recognition of substrate proteins carrying SUMO chains of variable length.
Asunto(s)
Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Dominios y Motivos de Interacción de Proteínas , Proteína SUMO-1/metabolismo , Sumoilación/fisiología , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Células HeLa , Humanos , Datos de Secuencia Molecular , Unión Proteica/fisiología , Dominios y Motivos de Interacción de Proteínas/fisiología , Saccharomyces cerevisiae , Especificidad por SustratoRESUMEN
We have recently reported that poly-SUMO-2/3 conjugates are subject to a ubiquitin-dependent proteolytic control in human cells. Here we show that arsenic trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. The SUMO-binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO. Reconstitution of SUMO-dependent ubiquitylation of PML by RNF4 in vitro and in a yeast trans vivo system revealed a preference of RNF4 for chain forming SUMOs. Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4.