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J Biol Chem. 2016 Dec 2;291(49):25516-25528. Epub 2016 Oct 25.

URI Regulates KAP1 Phosphorylation and Transcriptional Repression via PP2A Phosphatase in Prostate Cancer Cells.

Author information

  • 1From the Institute of Systems Genetics and.
  • 2the Departments of Biochemistry and Molecular Pharmacology.
  • 3the Department of Chemical Physiology, Scripps Research Institute, La Jolla, California 92037.
  • 4Urology, and.
  • 5the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and.
  • 6the Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109.
  • 7Microbiology at New York University School of Medicine, New York, New York 10016.
  • 8Urology, and susan.logan@nyumc.org.

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.

KEYWORDS:

phosphorylation; prostate cancer; protein phosphatase 2 (PP2A); transcription regulation; transcription repressor; unconventional prefoldin RPB5 interactor (URI)

PMID:
27780869
PMCID:
PMC5207251
[Available on 2017-12-02]
DOI:
10.1074/jbc.M116.741660
[PubMed - in process]
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