The serine/arginine-rich protein SF2/ASF regulates protein sumoylation.
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.
Pelisch
Federico
F
Laboratorio de Fisiología, Biología Molecular, Instituto de Fisiología, Biología Molecular, Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428EHA Buenos Aires, Argentina.
Gerez
Juan
J
Druker
Jimena
J
Schor
Ignacio E
IE
Muñoz
Manuel J
MJ
Risso
Guillermo
G
Petrillo
Ezequiel
E
Westman
Belinda J
BJ
Lamond
Angus I
AI
Arzt
Eduardo
E
Srebrow
Anabella
A
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
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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