UV-B/A irradiation of mouse keratinocytes results in p53-mediated WAF1/CIP1 expression.
The tumor suppressor gene p53 is involved in controlling cell cycle checkpoint or triggering apoptosis. p53 may accomplish these roles by acting as a sequence-specific transcription factor. One of the downstream targets of p53 transcription control is the WAF1/CIP1 gene, whose gene product p21 interacts with several cyclins and cyclin-dependent kinases, resulting in inhibition of these kinases. In our previous studies, we have shown that the p53 protein level in mouse keratinocytes was elevated following UV-B/A irradiation. In this paper we further investigated the consequences of increased p53 protein level by characterizing p53 DNA-binding level and WAF1/CIP1 gene expression in UV-B/A-irradiated mouse keratinocytes. Consistent with the increased level of p53 protein, both p53 DNA-binding level and steady-state level of WAF1/CIP1 mRNA were elevated. We have demonstrated that the induction of WAF1/CIP1 mRNA was mediated by p53, since no WAF1/CIP1 induction was observed in p53-deficient cells upon UV-B exposure. These observations suggest an important role for the tumor suppressor gene p53 in the response of keratinocytes to the biologically relevant UV-B/A irradiation and in suppressing UV-induced skin cancer.
Liu
M
M
Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha 68198, USA.
Pelling
J C
JC
D000818:Animals; D001483:Base Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016158:Genes, p53 / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA