Ultraviolet radiation induces phosphorylation and ubiquitin-mediated degradation of DeltaNp63alpha.

Westfall MD, Joyner AS, Barbieri CE, Livingstone M, Pietenpol JA
Cell Cycle. 2005 4 (5): 710-6

PMID: 15846104 · DOI:10.4161/cc.4.5.1685

DeltaNp63alpha, a homologue of the tumor suppressor p53, acts as a transcriptional repressor with dominant negative effects towards p53. Additionally, DeltaNp63alpha 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 DeltaNp63alpha posttranslational modification and stability in normal and transformed squamous epithelial cells. We found that DeltaNp63alpha protein levels decreased after ultraviolet radiation and paclitaxel treatment of both normal and transformed cells. After UV and paclitaxel treatment, DeltaNp63alpha phosphorylation was significantly modulated. Additionally, DeltaNp63alpha protein levels were regulated in a proteasome-dependent manner in control and UV treated cells with increased DeltaNp63alpha ubiquitination after UV treatment or proteasome inhibition. Our studies provide insight to a mechanism for DeltaNp63alpha regulation during normal cell proliferation and, in particular, after stress. Further, the inverse regulation of p53 and DeltaNp63alpha 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.

MeSH Terms (22)

Cell Line Cell Line, Tumor Cell Proliferation Cells, Cultured DNA-Binding Proteins Gene Expression Regulation Genes, p53 Genes, Tumor Suppressor Humans Keratinocytes Paclitaxel Phosphoproteins Phosphorylation Proteasome Endopeptidase Complex Proteasome Inhibitors Trans-Activators Transcription, Genetic Transcription Factors Tumor Suppressor Protein p53 Tumor Suppressor Proteins Ubiquitin Ultraviolet Rays

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