title: Regulation of protein translation and c-Jun expression by prostate tumor overexpressed 1.
abstract: Prostate tumor overexpressed-1 (PTOV1), a modulator of the Mediator transcriptional regulatory complex, is expressed at high levels in prostate cancer and other neoplasias in association with a more aggressive disease. Here we show that PTOV1 interacts directly with receptor of activated protein C kinase 1 (RACK1), a regulator of protein kinase C and Jun signaling and also a component of the 40S ribosome. Consistent with this interaction, PTOV1 was associated with ribosomes and its overexpression promoted global protein synthesis in prostate cancer cells and COS-7 fibroblasts in a mTORC1-dependent manner. Transfection of ectopic PTOV1 enhanced the expression of c-Jun protein without affecting the levels of c-Jun or RACK1 mRNA. Conversely, knockdown of PTOV1 caused significant declines in global protein synthesis and c-Jun protein levels. High levels of PTOV1 stimulated the motility and invasiveness of prostate cancer cells, which required c-Jun, whereas knockdown of PTOV1 strongly inhibited the tumorigenic and metastatic potentials of PC-3 prostate cancer cells. In human prostate cancer samples, the expression of high levels of PTOV1 in primary and metastatic tumors was significantly associated with increased nuclear localization of active c-Jun. These results unveil new functions of PTOV1 in the regulation of protein translation and in the progression of prostate cancer to an invasive and metastatic disease.
authors: Research Unit in Biomedicine, Translational and Pediatrics Oncology, Vall d'Hebron Institute of Research, Universidad Autónoma, Barcelona, Spain.
authors: N
authors: N
authors: Marqués
authors: Research Unit in Biomedicine, Translational and Pediatrics Oncology, Vall d'Hebron Institute of Research, Universidad Autónoma, Barcelona, Spain.
authors: M
authors: M
authors: Sesé
authors: Research Unit in Biomedicine, Translational and Pediatrics Oncology, Vall d'Hebron Institute of Research, Universidad Autónoma, Barcelona, Spain.
authors: V
authors: V
authors: Cánovas
authors: Research Unit in Biomedicine, Translational and Pediatrics Oncology, Vall d'Hebron Institute of Research, Universidad Autónoma, Barcelona, Spain.
authors: F
authors: F
authors: Valente
authors: 1] Department of Cell Biology, Institute for Molecular Biology, CSIC, Barcelona, Spain [2] Human and Experimental Functional Oncomorphology, Department of Pathology and Tumour Bank, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors: R
authors: R
authors: Bermudo
authors: Department of Pathology, Vall d'Hebron Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors: I
authors: I
authors: de Torres
authors: Functional Validation and Preclinical Research, Molecular Imaging Platform CIBBIM-Nanomedicine, Vall d'Hebron Institut de Recerca, Barcelona, Spain.
authors: Y
authors: Y
authors: Fernández
authors: Functional Validation and Preclinical Research, Molecular Imaging Platform CIBBIM-Nanomedicine, Vall d'Hebron Institut de Recerca, Barcelona, Spain.
authors: I
authors: I
authors: Abasolo
authors: Human and Experimental Functional Oncomorphology, Department of Pathology and Tumour Bank, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors: P L
authors: PL
authors: Fernández
authors: Laboratory of Molecular and Cellular Andrology, Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Santiago, Chile.
authors: H
authors: H
authors: Contreras
authors: Laboratory of Molecular and Cellular Andrology, Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Santiago, Chile.
authors: E
authors: E
authors: Castellón
authors: Department of Cell Biology, Institute for Molecular Biology, CSIC, Barcelona, Spain.
authors: T
authors: T
authors: Celià-Terrassa
authors: Institute for Research in Biomedicine, Parc Científic, University of Barcelona, Barcelona, Spain.
authors: R
authors: R
authors: Méndez
authors: Department of Pathology, Vall d'Hebron Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors: S
authors: S
authors: Ramón Y Cajal
authors: Department of Cell Biology, Institute for Molecular Biology, CSIC, Barcelona, Spain.
authors: T M
authors: TM
authors: Thomson
authors: Research Unit in Biomedicine, Translational and Pediatrics Oncology, Vall d'Hebron Institute of Research, Universidad Autónoma, Barcelona, Spain.
authors: R
authors: R
authors: Paciucci
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002522:Chlorocebus aethiops; D018450:Disease Progression; D004285:Dogs; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases