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Title

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

AuthorsBermudo, Raquel; Fernández, Pedro L.; Celià-Terrassa, Toni ; Thomson, Timothy M. ; Paciucci, Rosana
KeywordsPTOV1
c-Jun
Translation
Prostate cancer
Issue Date2013
PublisherNature Publishing Group
CitationOncogene: 1-11 (2013)
AbstractProstate 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.
DescriptionOncogene advance online publication.-- et al.
Publisher version (URL)http://dx.doi.org/10.1038/onc.2013.51
URIhttp://hdl.handle.net/10261/88212
DOI10.1038/onc.2013.51
ISSN0950-9232
E-ISSN1476-5594
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