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Rig is a novel Ras-related protein and potential neural tumor suppressor
Chad A Ellis1, Michele D Vos, Heather Howell
1Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 307, Rockville, MD 20850-3300, USA.
Abstract:
The Ras superfamily consists of a large group of monomeric GTPases demonstrating homology to Ras oncoproteins. Although structurally similar, Ras-superfamily proteins are functionally diverse. Whereas some members exhibit oncogenic properties, others may serve as tumor suppressors. We have identified a novel Ras-related protein that suppresses cell growth and have designated it Rig (Ras-related inhibitor of cell growth). Overexpression of Rig inhibited Ras-mediated cellular transformation and activation of downstream signaling in NIH 3T3 cells. rig mRNA is expressed at high levels in normal cardiac and neural tissue. However, Rig protein expression is frequently lost or down-regulated in neural tumor-derived cell lines and primary human neural tumors. Moreover, expression of exogenous Rig in human astrocytoma cells suppressed growth. Rig has a C-terminal CAAX motif that codes for posttranslational modification by both farnesyl and geranylgeranyl isoprenoid lipids. Consequently, Rig may play a role in the cellular response to farnesyl transferase inhibitors. Rig bears 63% overall sequence homology to a recently described Ras-family member Noey2, a tumor suppressor in breast and ovarian tissue. Therefore, Rig and Noey2 may represent a new subfamily of Ras-like tumor suppressors.
Insights
Researchers discovered Rig, a novel Ras-related protein that inhibits cell growth and transformation. Rig protein is downregulated in neural tumors, suggesting its role as a potential tumor suppressor.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- The Ras superfamily comprises diverse monomeric GTPases with varying roles, including oncogenesis and tumor suppression.
- Ras-related proteins share structural similarities but exhibit functional diversity.
Purpose of the Study:
- To identify and characterize novel Ras-related proteins involved in cell growth regulation.
- To investigate the role of Rig (Ras-related inhibitor of cell growth) in cellular transformation and tumor development.
Main Methods:
- Overexpression of Rig in NIH 3T3 cells to assess its effect on Ras-mediated transformation and signaling.
- Analysis of rig mRNA and Rig protein expression in normal tissues and neural tumors.
- Introduction of exogenous Rig into human astrocytoma cells to evaluate its impact on cell growth.
Main Results:
- Overexpression of Rig inhibited Ras-mediated cellular transformation and downstream signaling.
- Rig mRNA is highly expressed in cardiac and neural tissues.
- Rig protein expression was frequently lost or reduced in neural tumor cell lines and primary tumors.
- Exogenous Rig expression suppressed growth in human astrocytoma cells.
Conclusions:
- Rig functions as a suppressor of cell growth and transformation.
- Loss of Rig expression in neural tumors suggests its role as a tumor suppressor.
- Rig, with its C-terminal CAAX motif, may be involved in cellular responses to farnesyl transferase inhibitors.
- Rig and Noey2 may constitute a new subfamily of Ras-like tumor suppressors.