Chapter category: Cell Cycle

The Regulation of p53 Growth Suppression

This chapter appears in the following book:

Cell Cycle Checkpoints and Cancer

Edited by: Mikhail V. Blagosklonny
ISBN: 1-58706-067-1
» Get more information about this book at landesbioscience.com «

Chapter authors:
Ronit Vogt Sionov, Igal Louria Hayon, Ygal Haupt

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The p53 tumor suppressor protein plays a pivotal role in the cellular response to stress. A variety of stress signals trigger accumulation and activation of p53 to halt the cell cycle and to prevent replication of damaged DNA. The p53 protein is required for a proper G1 arrest, it is essential for maintaining the G2 arrest, and it contributes to the mitotic spindle checkpoint. p53 exerts these actions by inducing multiple target genes. Under defined conditions, p53 induces programmed cell death by mechanisms that are partially understood and involve a combination of transcriptional-dependent and —independent activities. The choice between arrest and cell death depends on the final integration of antagonistic signals. These include the type and intensity of the stress signal, the spectrum of the target genes induced, the type of cell and its oncogenic status, and the presence of growth and survival factors. The stability of the p53 protein and its activities are tightly regulated by many factors among which the Mdm2 proto-oncoprotein is the central player. Inhibitory effects of Mdm2 on p53 stability and activities are modulated by multiple mechanisms including post-translational modifications of p53 and Mdm2 and by other interacting proteins. Importantly, p53 is also regulated at the level of its sub-cellular localization. Sequestration of p53 into the cytoplasm is sufficient for its inhibition. In contrast, accumulation of p53 in the nucleus induces its transcriptional activity. This activity can be further enhanced by specific post-translational modifications and by recruitment of p53 into nuclear bodies. We discuss current views on the regulation of p53 and its growth inhibitory activities.

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Chapter category: Cell Cycle

The Regulation of p53 Growth Suppression

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