Identification of estrogen receptor ? as a SUMO-1 target reveals a novel phosphorylated sumoylation motif and regulation by glycogen synthase kinase 3?.

ABSTRACT: SUMO conjugation has emerged as a dynamic process in regulating protein function. Here we identify estrogen receptor ? (ER?) to be a new target of SUMO-1. ER? SUMO-1 modification occurs on a unique nonconsensus sumoylation motif which becomes fully competent upon phosphorylation of its contained serine residue, which provides the essential negative charge for sumoylation. This process is further regulated by phosphorylation of additional adjacent serine residues by glycogen synthase kinase 3? (GSK3?), which maximizes ER? sumoylation in response to hormone. SUMO-1 attachment prevents ER? degradation by competing with ubiquitin at the same acceptor site and dictates ER? transcriptional inhibition by altering estrogen-responsive target promoter occupancy and gene expression in breast cancer cells. These findings uncovered a novel phosphorylated sumoylation motif (pSuM), which consists of the sequence ?KXS (where ? represents a large hydrophobic residue) and which is connected to a GSK3-activated extension that functions as a SUMO enhancer. This extended pSuM offers a valuable signature to predict SUMO substrates under protein kinase regulation.

SUBMITTER: Picard N 

PROVIDER: S-EPMC3416183 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature