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A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M
Z Weng1, A C Fluckiger, S Nisitani
1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Abstract:
Cell cycle progression is monitored by highly coordinated checkpoint machinery, which is activated to induce cell cycle arrest until defects like DNA damage are corrected. We have isolated an anti-proliferative cell cycle regulator named G2A (for G2 accumulation), which is predominantly expressed in immature T and B lymphocyte progenitors and is a member of the seven membrane-spanning G protein-coupled receptor family. G2A overexpression attenuates the transformation potential of BCR-ABL and other oncogenes, and leads to accumulation of cells at G2/M independently of p53 and c-Abl. G2A can be induced in lymphocytes and to a lesser extent in nonlymphocyte cell lines or tissues by multiple stimuli including different classes of DNA-damaging agents and serves as a response to damage and cellular stimulation which functions to slow cell cycle progression.
Insights
Researchers identified G2A, a novel cell cycle regulator predominantly in immune progenitors. Overexpression of G2A halts cell cycle progression, suggesting its role in preventing uncontrolled cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Cell cycle checkpoints ensure genomic integrity by arresting progression upon detecting defects like DNA damage.
- The G protein-coupled receptor family plays diverse roles in cellular signaling and regulation.
Purpose of the Study:
- To isolate and characterize novel regulators of cell cycle progression.
- To investigate the function of a newly identified protein, G2A, in cell cycle control and oncogenesis.
Main Methods:
- Isolation and characterization of the G2A gene and protein.
- Overexpression studies in lymphocyte progenitor cell lines.
- Assessment of cell cycle distribution using flow cytometry.
- Analysis of oncogene transformation potential.
Main Results:
- G2A, a G protein-coupled receptor, is predominantly expressed in immature T and B lymphocyte progenitors.
- G2A overexpression induces cell cycle arrest at the G2/M phase, independent of p53 and c-Abl.
- G2A attenuates the transforming ability of oncogenes like BCR-ABL.
- G2A expression is induced by DNA-damaging agents and cellular stimulation, functioning as a cell cycle brake.
Conclusions:
- G2A is a novel anti-proliferative regulator of the cell cycle, particularly important in immune cell development.
- G2A acts as a safeguard against uncontrolled proliferation by inducing G2/M arrest in response to damage or stimulation.
- G2A represents a potential therapeutic target for controlling aberrant cell proliferation in cancer.