title: URI Regulates KAP1 Phosphorylation and Transcriptional Repression via PP2A Phosphatase in Prostate Cancer Cells.
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.
authors: From the Institute of Systems Genetics and.|the Departments of Biochemistry and Molecular Pharmacology.
authors: Paolo
authors: P
authors: Mita
authors: the Department of Chemical Physiology, Scripps Research Institute, La Jolla, California 92037.
authors: Jeffrey N
authors: JN
authors: Savas
authors: the Departments of Biochemistry and Molecular Pharmacology.
authors: Erica M
authors: EM
authors: Briggs
authors: Urology, and.|the Departments of Biochemistry and Molecular Pharmacology.
authors: Susan
authors: S
authors: Ha
authors: the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and.
authors: Veena
authors: V
authors: Gnanakkan
authors: the Department of Chemical Physiology, Scripps Research Institute, La Jolla, California 92037.
authors: John R
authors: JR
authors: Yates
authors: the Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors: Diane M
authors: DM
authors: Robins
authors: the Departments of Biochemistry and Molecular Pharmacology.
authors: Gregory
authors: G
authors: David
authors: From the Institute of Systems Genetics and.|the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and.|the Departments of Biochemistry and Molecular Pharmacology.
authors: Jef D
authors: JD
authors: Boeke
authors: Urology, and.|Microbiology at New York University School of Medicine, New York, New York 10016.
authors: Michael J
authors: MJ
authors: Garabedian
authors: Urology, and susan.logan@nyumc.org.|the Departments of Biochemistry and Molecular Pharmacology.
authors: Susan K
authors: SK
authors: Logan
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018626:Retroelements; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D018626:Retroelements; C117184:URI1 protein, human; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28; D054648:Protein Phosphatase 2
keywords: phosphorylation; prostate cancer; protein phosphatase 2 (PP2A); transcription regulation; transcription repressor; unconventional prefoldin RPB5 interactor (URI)