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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Roles of the transcription factor p53 in keratinocyte carcinomas
1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, USA. douglas.brash@yale.edu
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.
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