title: The serine/arginine-rich protein SF2/ASF regulates protein sumoylation.
abstract: Protein modification by conjugation of small ubiquitin-related modifier (SUMO) is involved in diverse biological functions, such as transcription regulation, subcellular partitioning, stress response, DNA damage repair, and chromatin remodeling. Here, we show that the serine/arginine-rich protein SF2/ASF, a factor involved in splicing regulation and other RNA metabolism-related processes, is a regulator of the sumoylation pathway. The overexpression of this protein stimulates, but its knockdown inhibits SUMO conjugation. SF2/ASF interacts with Ubc9 and enhances sumoylation of specific substrates, sharing characteristics with already described SUMO E3 ligases. In addition, SF2/ASF interacts with the SUMO E3 ligase PIAS1 (protein inhibitor of activated STAT-1), regulating PIAS1-induced overall protein sumoylation. The RNA recognition motif 2 of SF2/ASF is necessary and sufficient for sumoylation enhancement. Moreover, SF2/ASF has a role in heat shock-induced sumoylation and promotes SUMO conjugation to RNA processing factors. These results add a component to the sumoylation pathway and a previously unexplored role for the multifunctional SR protein SF2/ASF.
authors.affiliation: Laboratorio de Fisiología, Biología Molecular, Instituto de Fisiología, Biología Molecular, Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428EHA Buenos Aires, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Pelisch
authors.forename: Juan
authors.initials: J
authors.lastname: Gerez
authors.forename: Jimena
authors.initials: J
authors.lastname: Druker
authors.forename: Ignacio E
authors.initials: IE
authors.lastname: Schor
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Muñoz
authors.forename: Guillermo
authors.initials: G
authors.lastname: Risso
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Petrillo
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Westman
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arzt
authors.forename: Anabella
authors.initials: A
authors.lastname: Srebrow
mesh_terms: D002460:Cell Line; D018869:Heat-Shock Response; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D013379:Substrate Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; D000068103:Serine-Arginine Splicing Factors; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
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