Oncogene database

11315

PARK7

parkinson protein 7;PARK7;parkinson protein 7

Parkinson disease (autosomal recessive, early onset) 7|epididymis secretory sperm binding protein Li 67p|oncogene DJ1|protein DJ-1|protein deglycase DJ-1

1p36.23

protein-coding

Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in adult humans. Because the survival rate of patients with UM has changed little in the past few decades, a better understanding of the molecular events governing UM development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. In this study, we investigated UM tumour development by comparing two recently established UM cultures with different invasion potential by two-dimensional gel electrophoresis. Protein features expressed differentially were identified by mass spectrometric analysis. Potential markers were assayed in both cultures and in long-term established UM cell lines (UW-1, OCM-1, SP6.5 and 92.1) by Western blotting and their role in invasion analysed using Matrigel membranes. Comparative analysis revealed that UM cultures with low- and high-grade invasion potential differ in their cellular metabolism and, more interestingly, in several cancer-associated proteins, including those implicated in cell adhesion and migration, proliferation and various oncogenes. Our data indicate a correlation between MUC18 and HMG-1 expression and the invasiveness of UM cells. We also demonstrate the expression and secretion of DJ-1 oncoprotein by UM cells. We suggest a possible role for MUC18 and HMG-1 proteins in UM cell invasion. The secretion of DJ-1 by UM cells, and the ability to detect this protein in UM patients sera implicate it as a potential noninvasive biomarker for this malignancy.

Hepatocellular carcinoma (HCC) is a common malignant tumour. Development of HCC is a multi-step process from well-differentiated (G1), moderately differentiated (G2) to poorly differentiated (G3) phenotype. The early molecular modulators causing the onset of hepatocarcinogenesis are not fully understood. In the present study, we conducted comparative proteomics to analyze the differential proteome of G1 tumour and adjacent non-tumour tissues, with aims to identify the molecules as early tumour markers and to understand the early molecular events involved in initiation of tumorigenesis in hepatitis B virus (HBV)-infected G1 tumour. Differentially expressed proteins were identified by MALDI-TOF/TOF tandem mass spectrometry and NCBInr database interrogation. A total of 15 differentially expressed proteins with diverse biological functions were identified. Among these, 4 proteins were down-regulated, whereas the other 11 proteins were up-regulated in the G1 tumours. Two proteins, Proteasome activator subunit 1 (PA28alpha) and DJ-1, were firstly found to be down-regulated in HBV-infected G1 tumours. Down-regulations of these two proteins were further validated by Western blotting and immunohistochemistry in a panel of clinical specimens. These findings elucidate, at least in part, the molecular events underlying the mechanism and the potential roles of DJ-1 and PA28alpha in the onset of hepatocarcinogenesis.

We have isolated and characterized the cDNA encoding a novel protein designated DJ-1. DJ-1, sharing no significant homology with the sequences so far reported, did not show transactivation activity in the Gal4 recombinant system, but transformed mouse NIH3T3 cells by itself. Furthermore, DJ-1 showed a cooperative transforming activity with H-Ras, more than 3 times as strong as the activity of ras/myc combination. DJ-1 was ubiquitously expressed in various human tissues, and the expression was induced by growth stimuli. Moreover, DJ-1 translocated from cytoplasm to nuclei in the S phase of the cell cycle. DJ-1 is thus suggested to be a novel mitogen-dependent oncogene product involved in a Ras-related signal transduction pathway.