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Brief Report
CK2-site Phosphorylation of p53 is Induced in ΔNp63 Expressing Basal Stem Cells in UVB Irradiated Human Skin
Lee E. Finlan, Rudolf Nenutil, Sally H Ibbotson, Borek Vojtesek and Ted R. Hupp
volume 5 | issue 21
1 november 2006Pages: 2489 - 2494
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The activity of the tumour 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 tumour 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 p63αΔΝ is required for p53 activation after DNA damage, we examined and found a high proportion of cells co-express p63αΔΝ and CK2-phosphorylated p53 after UV-irradiation. As controls, the proliferation marker Ki67 and p63αΔΝ generally exhibit mutually exclusive expression. These data identify a physiological model with which to identify signalling pathways that mediate cross-talk between p63αΔΝ and activating p53 kinase pathways after DNA damage in basal cell populations.
Authors
Lee E. Finlan
The University of Edinburgh, Edinburgh, UK
Rudolf Nenutil
Masaryk Memorial Cancer Institute, Brno, Czech Republic
Sally H Ibbotson
The University of Dundee, Dundee, UK
Borek Vojtesek
Masaryk Memorial Cancer Institute, Brno, Czech Republic
Ted R. Hupp
The University of Edinburgh
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.