Classical and novel roles of p53 and prospects for anticancer therapy

The definitive version is available at http://www.sciencedirect.com/science/journal/14714914The tumor suppressor p53 is a transcription factor that is frequently inactivated in human tumors. Therefore,restoring its function has been considered an attractive approach to restrain cancer. Typically, p53-dependent growth arrest, senescence and apoptosis of tumor cells have been attributed to transcriptional activity of nuclear p53. Notably, wild-type p53 gain-of-function enhances cancer resistance in the mouse, but it also accelerates aging in some models, possibly due to altered p53 activity. Therefore, the emerging evidence of mitochondrial transcription-independent activities of p53 has raised high expectations. Here, we review new developments in transcription-dependent and transcription-independent p53 functions, recent advances in targeting p53 for cancer treatment and the pitfalls of moving from the laboratory research to the clinical setting.This Work in the laboratory of V.A. is supported by grants from Ministerio de Sanidad y Consumo/Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares RECAVA), from Sociedad Española de Cardiología, and from Ministerio de Educación y Ciencia and the European Regional Development Fund (SAF2004–03057). Work in the laboratory of U.M.M. is supported by the Nacional Cancer Institute and Philip Morris USA Inc. and Philip Morris International. J.J.F. is supported by a CSIC-I3P program pre-doctoral fellowship cosponsored by the European Social FundPeer reviewe