Disease relevance of PTOV1

• PTOV1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer [1].
• By immunohistochemical analysis, we have found that PTOV1 is overexpressed in 71% of 38 prostate carcinomas and in 80% of samples with prostate intraepithelial neoplasia [1].
• Semiquantitative RT-PCR has established that nine out of 11 tumors overexpress PTOV1 at levels significantly higher than benign prostatic hyperplasia or normal prostate tissue [2].
• In normal prostate tissue and in prostate adenomas, PTOV1 was undetectable or expressed at low levels, whereas nine out of 11 prostate adenocarcinomas showed a strong immunoreactivity, with a focal distribution in areas of carcinoma and prostatic intraepithelial neoplasia [2].
• These findings indicate that the PTOV1 gene is androgen-responsive in VSMCs and that it may play an important role in androgen-related atherogenesis in the human aorta, particularly early atherosclerosis in the male aorta, through regulating proliferation of neointimal VSMCs [3].

High impact information on PTOV1

• ARC92/ACID1 further contains a novel activator-interacting domain (ACID), which it shares with at least one other human gene termed PTOV1/ACID2 [4].
• Flotillin-1 colocalized with PTOV1 not only at the plasma membrane but, unexpectedly, also in the nucleus, as demonstrated by immunocytochemistry and subcellular fractionation of endogenous and exogenous flotillin-1 [5].
• Flotillin-1 entered the nucleus concomitant with PTOV1, shortly before the initiation of the S phase [5].
• These observations suggest that PTOV1 assists flotillin-1 in its translocation to the nucleus and that both proteins are required for cell proliferation [5].
• Protein levels of PTOV1 and flotillin-1 oscillated during the cell cycle, with a peak in S [5].

Biological context of PTOV1

• At the end of mitosis, PTOV1 exited the nucleus [1].
• The PTOV1 protein consists of two novel protein domains arranged in tandem, without significant similarities to known protein motifs [1].
• The human PTOV1 protein consists almost entirely of two repeated blocks of homology of 151 and 147 amino acids, joined by a short linker peptide, and is encoded by a 12-exon gene localized in chromosome 19q13 [2].
• Inhibition of PTOV1 by transfection of its corresponding siRNA suppressed testosterone-induced cell proliferation [3].
• 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 [1].

Anatomical context of PTOV1

• Immunocytochemical analysis and expression of chimeric GFP-PTOV1 proteins in cultured cells showed a predominantly perinuclear localization of PTOV1 [2].
• A 1.8-Kb PTOV1 transcript was detected abundantly in normal human brain, heart, skeletal muscle, kidney and liver, and at low levels in normal prostate [2].
• Both microarray and quantitative RT-PCR analyses demonstrated marked induction of the human prostate overexpressed protein 1 (PTOV1) gene by testosterone in the cell lines: this gene was recently identified as a novel androgen-induced gene involved in prostate tumour cell proliferation [3].

Associations of PTOV1 with chemical compounds

• PTOV1: a novel testosterone-induced atherogenic gene in human aorta [3].

Physical interactions of PTOV1

• We show here that PTOV1 interacts with the lipid raft protein flotillin-1, with which it copurifies in detergent-insoluble floating fractions [5].

Other interactions of PTOV1

• PTOV1 enables the nuclear translocation and mitogenic activity of flotillin-1, a major protein of lipid rafts [5].

References