Ultraviolet radiation-induced p53 responses in the epidermis are differentiation-dependent.
BACKGROUND
The tumour suppressor, p53, is recognized as a crucial molecule in regulating cellular responses to various DNA-damaging agents. Very early on in the development of nonmelanoma cancers p53 is mutated or lost, suggesting that p53 is crucial in protecting normal keratinocytes from the harmful effects of ultraviolet (UV) radiation.


OBJECTIVE
Using two mouse models, one with multiple copies of mutant p53 and the other a p53 "knockout," our laboratory has examined a role for p53 in UV-induced DNA damage and determined if these effects are differentiation dependent.


CONCLUSIONS
We outline in this review a proposed model reflecting differentiation-dependent p53 regulation of UV-induced responses in keratinocytes. After exposure to UV, basal keratinocytes repair damaged DNA, whereas differentiating keratinocytes undergo cell death, both processes are regulated by p53.
Tron
V A
VA
Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
Li
G
G
Ho
V
V
Trotter
M J
MJ
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair; D004817:Epidermis / Q000473:pathology / Q000528:radiation effects*; D016158:Genes, p53; D006801:Humans; D015603:Keratinocytes / Q000528:radiation effects*; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000502:physiology / Q000528:radiation effects*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D004247:DNA