Modulating the p53 pathway

p53 is a transcription factor that protects cells against stress, by modulating genes that induce growth arrest, repair, apoptosis, senescence or altered metabolism. Activation of p53 can potentially be used to modulate disease states. We describe here recent developments that attempt to modulate the function of p53 and outline strategies that are being investigated for pharmacological intervention in the p53 pathway. These include interruption of the interactions between p53 and its negative regulators, restabilization of mutant/misfolded p53, activation of p53 dependant transcription and modulation of p53 function systemically to affect the therapeutic profile of existing drugs. In addition the development of new animal models to investigate the above developments, including mice and zebrafish will be highlighted. (C) 2010 Elsevier Ltd. All rights reserved.