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Roles of the transcription factor p53 in keratinocyte carcinomas
Author(s) -
Brash D. E.
Publication year - 2006
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2006.07230.x
Subject(s) - keratinocyte , transcription factor , cancer research , downregulation and upregulation , apoptosis , biology , dna repair , dna damage , sunlight , mutant , cell cycle , tumor suppressor gene , dna , gene , carcinogenesis , cell culture , genetics , physics , astronomy
Summary 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.