Molecular "rehabilitation" by rational drug targeting: the challenge of P53 in cancer treatment.
The p53 tumor suppressor protein is a pivotal molecule in the protection against carcinogenesis and is inactivated in a plethora of human neoplasms, p53 prevents the accumulation of genomic alterations by inducing cell-cycle arrest or programmed cell death in response to genotoxic signals such as DNA damage and stress. In as much as p53 is a key modulator of cell proliferation, tight regulation of its function is critical for normal growth and homeostasis of cells and tissues. This is achieved by various mechanisms including the ability of the protein to adopt active and latent forms, its cellular localization, and control of p53 stability. The vast array of data on the atomic structure of the p53 protein, in conjunction with recent insights into the biochemical mechanisms that fine-tune its activity open up exciting new avenues for the development of rational therapeutic approaches aiming at restoring p53 function in a broad spectrum of human malignancies.
Tzatsos
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A
Department of Biochemistry, University of Patras School of Medicine, Greece.
Papavassiliou
A G
AG
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000502:physiology*
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53