URI regulates KAP1 phosphorylation and transcriptional repression via PP2A phosphatase in prostate cancer cells

Paolo Mita, Jeffrey N. Savas, Erica M. Briggs, Susan Ha, Veena Gnanakkan, John R. Yates, Diane M. Robins, Gregory David, Jef D. Boeke, Michael J. Garabedian, Susan K. Logan

    Research output: Contribution to journalArticle

    Abstract

    URI (unconventional prefoldin RPB5 interactor protein) is an unconventional prefoldin, RNA polymerase II interactor that functions as a transcriptional repressor and is part of a larger nuclear protein complex. The components of this complex and the mechanism of transcriptional repression have not been characterized. Here we show that KAP1 (KRAB-associated protein 1) and the protein phosphatase PP2A interact with URI. Mechanistically, we show that KAP1 phosphorylation is decreased following recruitment of PP2A by URI. We functionally characterize the novel URI-KAP1-PP2A complex, demonstrating a role of URI in retrotransposon repression, a key function previously demonstrated for the KAP1-SETDB1 complex. Microarray analysis of annotated transposons revealed a selective increase in the transcription of LINE-1 and L1PA2 retroelements upon knockdown of URI. These data unveil a new nuclear function of URI and identify a novel post-transcriptional regulation of KAP1 protein that may have important implications in reactivation of transposable elements in prostate cancer cells.

    Original languageEnglish (US)
    Pages (from-to)25516-25528
    Number of pages13
    JournalJournal of Biological Chemistry
    Volume291
    Issue number49
    DOIs
    StatePublished - Dec 2 2016

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    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Mita, P., Savas, J. N., Briggs, E. M., Ha, S., Gnanakkan, V., Yates, J. R., Robins, D. M., David, G., Boeke, J. D., Garabedian, M. J., & Logan, S. K. (2016). URI regulates KAP1 phosphorylation and transcriptional repression via PP2A phosphatase in prostate cancer cells. Journal of Biological Chemistry, 291(49), 25516-25528. https://doi.org/10.1074/jbc.M116.741660