Classic and novel roles of p53: prospects for anticancer therapy

The 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.