Alternative titles; symbols
HGNC Approved Gene Symbol: PTOV1
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38) : 19:49,850,705-49,860,742 (from NCBI)
Using differential display to identify genes upregulated in prostate tumors, followed by database analysis and RT-PCR, Benedit et al. (2001) cloned PTOV1. The deduced 416-amino acid protein consists almost entirely of 2 tandemly arranged blocks that share 66% identity and are joined by a short linker sequence. PTOV1 was predicted to form alternating alpha helices and beta sheets. Northern blot analysis detected a 1.8-kb transcript abundantly expressed in brain, heart, skeletal muscle, kidney, and liver. Normal prostate expressed low PTOV1 levels. Western blot analysis of prostate tumor tissue detected PTOV1 at an apparent molecular mass of 58 kD. Immunocytochemical analysis detected endogenous PTOV1 in the cytoplasm, concentrated around the nucleus.
Benedit et al. (2001) found that PTOV1 was overexpressed in 9 of 11 prostate tumor samples. It was markedly overexpressed in foci of prostate tumors with malignant morphology, and it was modestly elevated, but with a homogeneous distribution, in morphologically normal cells located in benign peripheral zones of the same tumors. In a human prostate carcinoma cell line, expression of PTOV1 increased following exposure to 5-alpha-dihydroxytestosterone.
By immunohistochemical analysis, Santamaria et al. (2003) found that PTOV1 was overexpressed in 71% of 38 prostate carcinomas and in 80% of samples with prostate intraepithelial neoplasia. High levels of PTOV1 in tumors correlated significantly with proliferative index and localization of PTOV1 in the nucleus. In quiescent cultured prostate tumor cells, PTOV1 localized to the cytoplasm and was excluded from nuclei. After serum stimulation, PTOV1 partially translocated to the nucleus at the beginning of S phase. At the end of mitosis, PTOV1 exited the nucleus. Transient transfection of fluorescence-tagged PTOV1 forced entry of cells into S phase and increased expression of cyclin D1 (CCND1; 168461).
Santamaria et al. (2005) found that PTOV1 interacted with the lipid raft protein flotillin-1 (FLOT1; 606998) in detergent-insoluble membrane fractions. Flotillin-1 colocalized with PTOV1 at the plasma membrane and in the nucleus, and it entered the nucleus concomitant with PTOV1 shortly before initiation of S phase. Protein levels of PTOV1 and flotillin-1 oscillated during the cell cycle, with a peak in S phase. Depletion of PTOV1 significantly inhibited nuclear localization of flotillin-1, whereas depletion of flotillin-1 did not affect nuclear localization of PTOV1. Depletion of either protein markedly inhibited cell proliferation under basal conditions. Overexpression of PTOV1 or flotillin-1 strongly induced proliferation, which required their localization to the nucleus and was dependent on the reciprocal protein. Santamaria et al. (2005) concluded that PTOV1 assists flotillin-1 in its translocation to the nucleus and that both proteins are required for cell proliferation.
Benedit et al. (2001) determined that the PTOV1 gene contains 12 exons.
By FISH, Benedit et al. (2001) mapped the PTOV1 gene to chromosome 19q13.3-q13.4.
Benedit, P., Paciucci, R., Thomson, T. M., Valeri, M., Nadal, M., Caceres, C., de Torres, I., Estivill, X., Lozano, J. J., Morote, J., Reventos, J. PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks. Oncogene 20: 1455-1464, 2001. [PubMed: 11313889] [Full Text: https://doi.org/10.1038/sj.onc.1204233]
Santamaria, A., Castellanos, E., Gomez, V., Benedit, P., Renau-Piqueras, J., Morote, J., Reventos, J., Thomson, T. M., Paciucci, R. PTOV1 enables the nuclear translocation and mitogenic activity of flotillin-1, a major protein of lipid rafts. Molec. Cell. Biol. 25: 1900-1911, 2005. [PubMed: 15713644] [Full Text: https://doi.org/10.1128/MCB.25.5.1900-1911.2005]
Santamaria, A., Fernandez, P. L., Farre, X., Benedit, P., Reventos, J., Morote, J., Paciucci, R., Thomson, T. M. PTOV-1, a novel protein overexpressed in prostate cancer, shuttles between the cytoplasm and the nucleus and promotes entry into the S phase of the cell division cycle. Am. J. Path. 162: 897-905, 2003. [PubMed: 12598323] [Full Text: https://doi.org/10.1016/S0002-9440(10)63885-0]