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Ras and Rho regulation of the cell cycle and oncogenesis
1University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Department of Pharmacology, Chapel Hill, NC 27599-7295, USA.
Abstract:
The important contribution of aberrant Ras activation in oncogenesis is well established. Our knowledge of the signaling pathways that are regulated by Ras is considerable. However, the number of downstream effectors of Ras continues to increase and our understanding of the role of these effector signaling pathways in mediating oncogenesis is far from complete and continues to evolve. Similarly, our understanding of the components that control mitogen-stimulated cell cycle progression is also very advanced. Where our understanding has lagged has been the delineation of the mechanism by which Ras causes a deregulation of cell cycle progression to promote the uncontrolled proliferation of the cancer cell. In this review, we summarize our current knowledge of how deregulated Ras activation alters the function of cyclin D1, p21(Cip1), and p27(Kip1). The two themes that we have emphasized are the involvement of Rho small GTPases in cell cycle regulation and the cell-type differences in how Ras signaling interfaces with the cell cycle machinery.
Insights
Aberrant Ras activation drives cancer by disrupting cell cycle control. This review details how Ras impacts cyclin D1, p21(Cip1), and p27(Kip1), highlighting Rho GTPases and cell-type variations in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Aberrant Ras activation is a key driver of oncogenesis.
- Ras signaling pathways are extensively studied, but downstream effectors and their roles in cancer are still evolving.
- Mitogen-stimulated cell cycle control is well understood, yet the precise mechanisms of Ras-induced cell cycle deregulation remain unclear.
Purpose of the Study:
- To review current knowledge on how deregulated Ras activation affects cell cycle regulators.
- To emphasize the role of Rho small GTPases in Ras-mediated cell cycle control.
- To explore cell-type specific differences in Ras signaling's interface with the cell cycle machinery.
Main Methods:
- Literature review of Ras signaling in oncogenesis and cell cycle regulation.
- Focus on alterations in cyclin D1, p21(Cip1), and p27(Kip1) function due to Ras.
- Analysis of the involvement of Rho small GTPases and cell-type specific mechanisms.
Main Results:
- Deregulated Ras signaling alters the function of key cell cycle proteins like cyclin D1, p21(Cip1), and p27(Kip1).
- Rho small GTPases play a significant role in mediating Ras's effects on cell cycle progression.
- Cell-type specific differences exist in how Ras signaling interacts with the cell cycle machinery.
Conclusions:
- Understanding Ras-induced cell cycle deregulation is crucial for cancer therapy.
- Rho GTPases and cell-type specific responses are important considerations in Ras-driven oncogenesis.
- Further research into these mechanisms can reveal novel therapeutic targets for cancers with aberrant Ras activation.