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DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras
D Nagakubo1, T Taira, H Kitaura
1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Biochemical and Biophysical Research Communications
|February 13, 1997
Summary
We discovered a novel oncogene, DJ-1, that transforms cells and works with H-Ras. Its expression increases with growth signals, and it moves to the nucleus during cell division, suggesting a role in cell growth pathways.
Area of Science:
- Molecular Biology
- Oncology
- Cell Signaling
Background:
- The identification of novel oncogenes is crucial for understanding cancer development.
- Signal transduction pathways, particularly those involving Ras, play a key role in cell proliferation and oncogenesis.
Purpose of the Study:
- To isolate and characterize a novel protein, DJ-1, and investigate its potential role in cell transformation and oncogenesis.
- To elucidate the function and cellular localization of DJ-1 in relation to cell cycle and growth stimuli.
Main Methods:
- cDNA isolation and characterization.
- Cell transformation assays using NIH3T3 cells, including co-transformation with H-Ras.
- Western blot analysis to determine tissue expression and cellular localization.
- Gal4 recombinant system to assess transactivation activity.
Main Results:
- A novel protein, DJ-1, was isolated and characterized, showing no significant homology to known sequences.
- DJ-1 demonstrated potent transforming activity in NIH3T3 cells, both independently and cooperatively with H-Ras.
- DJ-1 expression was found to be ubiquitous in human tissues and induced by growth stimuli.
- DJ-1 translocated from the cytoplasm to the nucleus during the S phase of the cell cycle.
Conclusions:
- DJ-1 is a novel mitogen-dependent oncogene product.
- DJ-1 is involved in a Ras-related signal transduction pathway, contributing to cell transformation.
- The cell cycle-dependent nuclear translocation of DJ-1 suggests a role in regulating cell proliferation.