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Nuclear Ras: unexpected subcellular distribution of oncogenic forms
G Wurzer1, W Mosgoeller, M Chabicovsky
1Institute of Cancer Research, University of Vienna, A-1090 Vienna, Austria.
Journal of Cellular Biochemistry. Supplement
|July 17, 2001
Summary
Activated Harvey-ras (H-Ras) oncogenes, involved in human cancers, unexpectedly localize to the nucleus. This nuclear transport, mediated by NTF2, impacts cell cycle regulation and may play a role in oncogenic activation or apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The Harvey-ras (H-Ras) gene encodes proteins crucial for cell signaling.
- Mutant H-Ras forms are implicated in various human cancers.
- Proper post-translational processing is essential for H-Ras function and localization.
Purpose of the Study:
- To investigate the subcellular localization of activated H-Ras (Val 12).
- To explore the mechanism and implications of H-Ras nuclear localization in cancer cells.
Main Methods:
- Immunofluorescence microscopy to visualize H-Ras localization.
- Immunoblot analysis of nuclear fractions.
- Inhibition of protein farnesylation.
- Analysis of cell cycle inhibitor p27.
- Co-immunoprecipitation with nuclear transport factor 2 (NTF2).
Main Results:
- Activated H-Ras (Val 12) was found in both the cytoplasm and nucleus of transformed cells.
- Nuclear targeting of H-Ras was dependent on protein farnesylation.
- Nuclear H-Ras correlated with altered p27 phosphorylation and subcellular distribution.
- H-Ras was observed to complex with NTF2, a nuclear transport factor.
Conclusions:
- Activated H-Ras exhibits nuclear localization in addition to its known cytoplasmic presence.
- Protein farnesylation is critical for the nuclear import of activated H-Ras.
- NTF2 may serve as the carrier for oncogenic Ras nuclear transport.
- The functional significance of nuclear H-Ras in oncogenesis and apoptosis warrants further investigation.