Regulation of protein translation and c-Jun expression by prostate tumor overexpressed 1

N. Marqués, M. Sesé, V. Cánovas, F. Valente, R. Bermudo, I. De Torres, Y. Fernández, I. Abasolo, P. L. Fernández, H. Contreras, E. Castellón, T. Celià-Terrassa, R. Méndez, S. Ramón Y Cajal, T. M. Thomson, R. Paciucci

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22 Citations (Scopus)

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. © 2014 Macmillan Publishers Limited.
Original languageEnglish
Pages (from-to)1124-1134
JournalOncogene
Volume33
Issue number9
DOIs
Publication statusPublished - 27 Feb 2014

Keywords

  • c-Jun
  • invasion
  • prostate cancer
  • PTOV1
  • translation

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