The serine/arginine-rich protein SF2/ASF regulates protein sumoylation

Federico Pelisch, Juan Gerez, Jimena Druker, Ignacio E. Schor, Manuel J. Munoz, Guillermo Risso, Ezequiel Petrillo, Belinda J. Westman, Angus I. Lamond, Eduardo Arzt, Anabella Srebrow

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    38 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)16119-16124
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume107
    Issue number37
    DOIs
    Publication statusPublished - 14 Sep 2010

    Keywords

    • posttranslational modification
    • splicing factor
    • RNA processing
    • E3 ligase
    • SPLICING FACTOR ASF/SF2
    • HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS
    • HUMAN TOPOISOMERASE-I
    • MESSENGER-RNA
    • SR PROTEINS
    • SUMO MODIFICATION
    • GENE-EXPRESSION
    • E3 LIGASE
    • TRANSLATION INITIATION
    • PROTEOMIC ANALYSIS

    Cite this

    Pelisch, F., Gerez, J., Druker, J., Schor, I. E., Munoz, M. J., Risso, G., Petrillo, E., Westman, B. J., Lamond, A. I., Arzt, E., & Srebrow, A. (2010). The serine/arginine-rich protein SF2/ASF regulates protein sumoylation. Proceedings of the National Academy of Sciences of the United States of America, 107(37), 16119-16124. https://doi.org/10.1073/pnas.1004653107