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.
Fuster
José J
JJ
Vascular Biology Unit, Instituto de Biomedicina de Valencia (IBV-CSIC), Spanish Council for Scientific Research, 46010 Valencia, Spain.
Sanz-González
Silvia M
SM
Moll
Ute M
UM
Andrés
Vicente
V
D000375:Aging / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D051020:bcl-X Protein / Q000502:physiology
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein