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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Oncoprotein signalling and mitosis
1Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA.
Abstract:
Studies of the roles of oncoproteins in cell cycle progression have concentrated on G1 because transformation is frequently associated with loss of G1 checkpoint control. However, it has become evident that G2 and mitotic checkpoints are often compromised in transformed cells and that many tumour suppressor proteins and oncoprotein kinases regulate and/or are activated in G2 and M. Disruption of p53 and ATM tumour suppressor protein functions can eliminate G2 and M checkpoints. The Src family kinases are activated in mitosis and collectively play an indispensable role in progression through G2/M. In addition, evidence suggests that Mos and elements of the Ras/Raf/MAPK cascade are also active in mitosis and appear likely to regulate G2 and/or M. Potential targets of these kinases include likely regulators of gene expression and microtubule dynamics such as Sam68 and Oncoprotein 18/stathmin. The ability of some oncoproteins to perturb orderly progression through both G1 and/or S and G2 and/or M is probably important for transformation.
Insights
Oncoproteins can disrupt cell cycle checkpoints, particularly in the G2 and M phases, which is crucial for cancer development. Understanding these disruptions aids in targeting cancer progression.
Area of Science:
- Cell Biology
- Molecular Oncology
- Cancer Research
Background:
- Cell cycle progression is tightly regulated by checkpoints, with a focus on G1 phase control in cancer research.
- Transformed cells often exhibit compromised G2 and mitotic checkpoints, involving tumor suppressor proteins and oncoprotein kinases.
- Key regulators like p53, ATM, Src family kinases, and the Ras/Raf/MAPK pathway are implicated in G2/M phase regulation.
Purpose of the Study:
- To investigate the roles of oncoproteins in G2 and M phase cell cycle regulation.
- To explore how disruptions in G2/M checkpoints contribute to cellular transformation.
- To identify potential targets of oncoproteins involved in mitotic progression.
Main Methods:
- Analysis of cell cycle checkpoint regulation in transformed cells.
- Investigating the activity and targets of specific oncoproteins and kinases during G2/M phase.
- Review of existing literature on tumor suppressor proteins and oncoprotein functions in mitosis.
Main Results:
- G2 and mitotic checkpoints are frequently compromised in cancer cells.
- Oncoprotein kinases like Src family kinases, Mos, and MAPK pathway elements are active and crucial during G2/M.
- Potential targets include gene expression regulators (Sam68) and microtubule dynamics regulators (Oncoprotein 18/stathmin).
Conclusions:
- Oncoproteins play a significant role in regulating and potentially disrupting G2 and M phase progression.
- Perturbation of G2/M checkpoints by oncoproteins is a key mechanism contributing to cellular transformation and cancer.
- Targeting these oncoproteins and their downstream effectors may offer therapeutic strategies for cancer treatment.
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