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Updated: Jun 8, 2026

Detection of Protein Ubiquitination
Published on: August 19, 2009
The E3 ubiquitin ligase WWP1 regulates ΔNp63-dependent transcription through Lys63 linkages
Angelo Peschiaroli1, Flavia Scialpi, Francesca Bernassola
1IDI IRCCS Biochemistry Laboratory, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Abstract:
The transcription factor p63, a member of the p53 family, plays a crucial role in epithelial development and tumorigenesis through the regulation of epithelial progenitor cell proliferation, differentiation and apoptosis. Similarly to p53, p63 activity is regulated by post-translational modifications, including ubiquitylation. Here, we report that the WWP1 E3 ubiquitin ligase binds specifically to ΔNp63 isoform but it does not trigger ΔNp63 proteasome-dependent degradation. Accordingly, we found that WWP1-dependent ubiquitylation of ΔNp63 occurs through the formation of Lys63-linked poly-ubiquitin chains. Importantly, we found that WWP1 is able to increase ΔNp63-dependent transcription and depletion of WWP1 in human primary keratinocytes induces cell cycle arrest. All together these results indicate that WWP1 regulates ΔNp63 transcriptional activity, acting thus as a potential regulator of the proliferation and survival of epithelial-derived cells.
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