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p53 and cell-cycle control: a finger in every pie
Abstract:
The p53 protein plays diverse, complementary roles in the regulation of cell proliferation, genetic integrity and survival after exposure to various forms of genotoxic and non-genotoxic stresses. While there is considerable in vivo evidence that induction of apoptosis in response to DNA damage is an important biological response mediated by p53, the physiological role of p53 in the control of the cell cycle is still poorly understood. In this review, we first discuss evidence showing that p53 expression, protein level and activity are regulated in a cell-cycle dependent manner (by transcriptional control, control of protein stability, and changes in phosphorylation, acetylation and protein conformation). We then summarize the data available on the direct or indirect involvement of p53 in the control of cell-cycle progression in G1, S, G2 and M phases. Based on recent in vitro and in vivo data, we suggest that permanent cell-cycle arrest may represent a response to stress in cells with limited proliferative potential, which allows both genetic and tissular integrity to be preserved. We also discuss the way in which cell-cycle regulation may contribute to control p53 protein levels and activity during the normal cell cycle.
Insights
The p53 protein regulates cell proliferation, genetic integrity, and survival. This review explores p53
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The p53 protein is crucial for cellular responses to stress, including DNA damage.
- Its roles in cell cycle control are not fully understood, despite evidence for its involvement in apoptosis.
Purpose of the Study:
- To review the cell-cycle-dependent regulation of p53 expression, protein levels, and activity.
- To summarize p53's involvement in controlling progression through G1, S, G2, and M phases.
- To discuss how cell-cycle regulation impacts p53 activity and levels during the normal cell cycle.
Main Methods:
- Review of existing in vitro and in vivo data.
- Analysis of transcriptional control, protein stability, and post-translational modifications (phosphorylation, acetylation, conformation).
Main Results:
- p53 expression, protein levels, and activity are modulated in a cell-cycle-dependent manner.
- p53 directly or indirectly influences progression through all phases of the cell cycle (G1, S, G2, M).
- Permanent cell-cycle arrest is proposed as a stress response in cells with limited proliferative potential.
Conclusions:
- p53 plays a significant role in cell cycle control, maintaining genetic and tissue integrity.
- Cell-cycle regulation is a key mechanism for controlling p53 protein levels and activity.
- Understanding p53's cell cycle functions is vital for comprehending cellular responses to stress.