title: Identification of estrogen receptor β as a SUMO-1 target reveals a novel phosphorylated sumoylation motif and regulation by glycogen synthase kinase 3β.
abstract: SUMO conjugation has emerged as a dynamic process in regulating protein function. Here we identify estrogen receptor β (ERβ) to be a new target of SUMO-1. ERβ 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 3β (GSK3β), which maximizes ERβ sumoylation in response to hormone. SUMO-1 attachment prevents ERβ degradation by competing with ubiquitin at the same acceptor site and dictates ERβ 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 ψKXS (where ψ 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.
authors.affiliation: Sainte-Justine Hospital Research Center, University of Montreal, Montréal, Québec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Picard
authors.forename: Véronique
authors.initials: V
authors.lastname: Caron
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bilodeau
authors.forename: Mélanie
authors.initials: M
authors.lastname: Sanchez
authors.forename: Xavier
authors.initials: X
authors.lastname: Mascle
authors.forename: Muriel
authors.initials: M
authors.lastname: Aubry
authors.forename: André
authors.initials: A
authors.lastname: Tremblay
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D058207:Sumoylation
chemical_list: D047629:Estrogen Receptor beta; D050505:Mutant Proteins; D011994:Recombinant Proteins; D025842:SUMO-1 Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3