PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks

Abstract

In a search for molecular markers of progression in prostate cancer by means of di erential display, we have identi®ed a new gene, which we have designated PTOV1. Semiquantitative RT ± PCR has established that nine out of 11 tumors overexpress PTOV1 at levels signi®cantly higher than benign prostatic hyperplasia or normal prostate tissue. 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 19q13.3. A Drosophila melanogaster PTOV1 homolog also contains two tandemly arranged PTOV blocks. A second gene, PTOV2, was identi®ed in humans and Drosophila, coding for proteins with a single PTOV homology block and unrelated amino-and carboxyl-terminal extensions. 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. Immunocytochemical analysis and expression of chimeric GFP-PTOV1 proteins in cultured cells showed a predominantly perinuclear localization of PTOV1. 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. Therefore, PTOV1 is a previously unknown gene, overexpressed in early and late stages of prostate cancer. The PTOV homology block represents a new class of conserved sequence blocks present in human, rodent and¯y proteins. Oncogene (2001) 20, 1455 ± 1464.

Structure and VP16 binding of the Mediator Med25 activator interaction domain

“…6). However, there are two domains with a fold that resembles that of Med25 ACID in another human protein, PTOV1, which is overexpressed in prostate cancers 48 and is involved in cell proliferation 49 ( Supplementary Fig. 4).…”

The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator

“…ARC92 exhibits homologs in higher eukaryotes, including frog, zebrafish, fruit f ly, and plants; however, we have been unable to identify homologs in Caenorhabditis elegans or yeast, suggesting that ARC92 may either have diverged during evolution or that it has emerged as a subunit in higher eukaryotes in response to the demands imposed by an increasingly complex gene regulatory apparatus (data not shown). A homology search also revealed that a segment of ARC92 appears to be highly related to a repeated sequence in a protein of unknown function that was identified based on its overexpression in prostate tumors (PTOV1) (26) (Fig. 1B).…”

Is There a Role for Prostate Tumour Overexpressed-1 in the Diagnosis of HGPIN and of Prostatic Adenocarcinoma? A Comparison with α-Methylacyl CoA Racemase

“…Transient transfection of chimeric green fluorescent protein-PTOVI forces the entry of cells into the S phase ofthe cell cycle, as shown by double fluorescent imaging for green fluorescent protein and for Ki67, and also by flow cytometry. These observations suggest that PTOVI contribute to the proliferative status of cells (1,4,5).…”

“…It has been suggested that overexpression of PTOVI can contribute to the proliferative status of prostate tumour cells and thus to their biological behaviour (1)(2)(3)(4)(5). The protein PTOVI is overexpressed immunohistochemically in over 70% of PCa cases (3,5).…”