Roles of the transcription factor p53 in keratinocyte carcinomas

DE Brash - British Journal of Dermatology, 2006 - academic.oup.com
British Journal of Dermatology, 2006academic.oup.com
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 …
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.
Oxford University Press