title: Roles of the transcription factor p53 in keratinocyte carcinomas.
abstract: The transcription factor p53 is mutated in most keratinocyte carcinomas (nonmelanoma skin cancers). In these tumours, the gene bears the trace of its mutagen, sunlight. Sunlight-induced p53 mutations are also seen in skin precancers and even sun-exposed skin, which harbours thousands of p53-mutant keratinocyte clones. Normal p53 is upregulated by sunlight exposure, after which it acts as a tumour suppressor in several ways: increasing DNA repair, arresting the cell cycle and inducing apoptosis of badly damaged keratinocytes. This UV-induced upregulation has been used as an assay for assessing the effectiveness of sunscreens. Once mutated, however, p53 renders cells apoptosis-resistant and therefore less sensitive to sunlight overexposure than normal cells. This reversal of roles drives clonal expansion of precancerous keratinocytes.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, USA. douglas.brash@yale.edu
authors.forename: D E
authors.initials: DE
authors.lastname: Brash
mesh_terms: D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004260:DNA Repair; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D012878:Skin Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53