SUMO-triggered ubiquitination of NR4A1 controls macrophage cell death.

ABSTRACT: Nuclear receptor NR4A1 has been implicated as a key regulator in a wide range of pathophysiological responses. As an immediate early response gene, NR4A1 can be rapidly and potently induced by a variety of stimuli. Its induction is followed by its rapid degradation, but the mechanism by which NR4A1 is degraded remains poorly understood. Here we show that nuclear receptor NR4A1 is sumoylated by SUMO2/3. Upon poly-SUMO modification, NR4A1 can be targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation. The SUMO E3 ligase PIAS3 promotes SUMOylation and polyubiquitination of NR4A1, while the SUMO protease SENP1 acts to de-conjugate SUMO. We demonstrate that this pathway is important for rapid degradation of NR4A1 after induced by stress. Moreove

SUBMITTER: Zhang L 

PROVIDER: S-EPMC5563982 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature