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Ultraviolet Radiation Induces Phosphorylation and Ubiquitin-Mediated Degradation of ΔNP63α
Matthew D. Westfall, Amanda S. Joyner, Christopher E. Barbieri, Mark Livingstone and Jennifer A. Pietenpol
volume 4 | issue 5
may 2005Pages: 710-716
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ΔNP63α, a homologue of the tumor suppressor p53, acts as a transcriptional repressor with dominant negative effects towards p53. Additionally, ΔNP63α is overexpressed in a number of squamous cell carcinomas, suggesting a potential role in oncogenesis. However, the mechanisms regulating p63 have yet to be elucidated. The goal of the current study was to determine the effect of various genotoxic stresses on ΔNP63α posttranslational modification and stability in normal and transformed squamous epithelial cells. We found that ΔNP63α protein levels decreased after ultraviolet radiation and paclitaxel treatment of both normal and transformed cells. After UV and paclitaxel treatment, ΔNP63αphosphorylation was significantly modulated. Additionally, ΔNP63α protein levels were regulated in a proteasome-dependent manner in control and UV treated cells with increased ?Np63? ubiquitination after UV treatment or proteasome inhibition. Our studies provide insight to a mechanism for ΔNP63α regulation during normal cell proliferation and, in particular, after stress. Further, the inverse regulation of p53 and ΔNP63α protein levels after cell stress through opposing regulation of proteasome-mediated degradation may allow for rapid transcriptional changes of specific target genes that are consistent with the roles of these family members in tumor suppression and cell growth.
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.