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Targeting p21-Dependent Pathways for Cell Death in Cancer Therapy

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Checkpoint Controls and Targets in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Checkpoint activation is a natural response to DNA damage that enables cells to take approp-riate action, which results in cells either living or dying. A major target in checkpoint response is the tumor suppressor p53, which becomes stabilized and activated following the post-translation modifications. The activated p53 then transactivates the downstream p21 gene to inhibit cyclin-dependent kinase (CDK), induce cell cycle arrest to allow DNA repair, and enable cells to survive. If DNA damage is excessive, then p53-dependent apoptosis is affected. Since cell cycle arrest precedes cell death, it is not surprising that checkpoint response has been correlated with apoptosis, and the possibility that these two processes cross-communicate is supported by evidence that p21, like p53, is a tumor suppressor, and its expression is downregulated in apoptosis-defective cancers. In addition to affecting apoptosis through checkpoint response, p21 can also induce this mode of cell death through a different mechanism that involves repression of anti-apoptotic genes. It becomes apparent that p21 may be an important component of not only checkpoint response, but also apoptosis.

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Supported by NIH Grant RO1 CA127263.

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  1. Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Zahid H. Siddik Ph.D.

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  1. M.D. Anderson Cancer Center, University of Texas, Holcombe Blvd. 1515, Houston, 77030, U.S.A.

    Zahid H. Siddik

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Siddik, Z.H. (2010). Targeting p21-Dependent Pathways for Cell Death in Cancer Therapy. In: Siddik, Z. (eds) Checkpoint Controls and Targets in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60761-178-3_13

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