Gene-specific mechanisms of p53 transcriptional control and prospects for cancer therapy.

The regulation of gene-specific activation is critical to the tumor suppressor function by p53. p53 is a well-characterized transcription factor that responds to DNA damage and other genotoxic stresses by the activation of downstream targets that are involved with repair, differentiation, senescence, growth arrest, and apoptosis. Sequence-specific binding to DNA, conformation, post-translational modifications, cofactor binding, stability, and subcellular localization all influence the performance of p53. The purpose of this review is to define features that play a key role in gene-specific activation and to show that these are often incapacitated in cancer cells. Using such knowledge to design selective strategies for the restoration of p53 wild-type function in cancer cells represents a promising cancer therapy. 2006 Wiley-Liss, Inc.