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.
Resnick-Silverman
Lois
L
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
Manfredi
James J
JJ