The activity of the tumor suppressor protein p53 is controlled by a balance between E3-ligase mediated p53 protein degradation and protein kinase-mediated assembly of p53:p300 transcription machinery. Genetic studies in mice have shown that mutation of the CK2 phospho-acceptor site in p53 increases UV-induced skin cancer formation,(11) highlighting an unexpected role for p53 phosphorylation in mediating p53-dependent tumor suppression. However, it is not known in which cell types CK2-mediated phosphorylation of p53 occurs. Using human skin as a model to determine whether there is cell-selectivity in modulating p53 phosphorylation, we have found a selective induction of p53 phosphorylation at the CK2-site in the basal cells of UV irradiated human skin. Dual-immunofluorescence also revealed that Ser392 and Ser15 phosphorylation of p53 also occur in the same basal cells, although often within distinct regions of the nucleus. Given that p63alphaDeltaN is required for p53 activation after DNA damage, we examined and found a high proportion of cells co-express p63alphaDeltaN and CK2-phosphorylated p53 after UV-irradiation. As controls, the proliferation marker Ki67 and p63alphaDeltaN generally exhibit mutually exclusive expression. These data identify a physiological model with which to identify signaling pathways that mediate cross-talk between p63alphaDeltaN and activating p53 kinase pathways after DNA damage in basal cell populations.

• MeSH
• DNA vazebné proteiny metabolismus   MeSH
• fosforylace MeSH
• kaseinkinasa II * fyziologie   MeSH
• kmenové buňky cytologie   metabolismus   MeSH
• kůže * metabolismus   účinky záření   MeSH
• lidé MeSH
• myši MeSH
• nádorové supresorové proteiny metabolismus   MeSH
• nádorový supresorový protein p53 chemie   metabolismus   MeSH
• poškození DNA MeSH
• progrese nemoci MeSH
• regulace genové exprese * MeSH
• signální transdukce MeSH
• trans-aktivátory metabolismus   MeSH
• transkripční faktory MeSH
• ubikvitinligasy metabolismus   MeSH
• ultrafialové záření MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH