The E3 ubiquitin ligase WWP1 regulates ΔNp63-dependent transcription through Lys63 linkages

Angelo Peschiaroli, Flavia Scialpi, Francesca Bernassola, El Said El Sherbini, Gerry Melino

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)425-430
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume402
Issue number2
DOIs
Publication statusPublished - Nov 12 2010

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Keywords

  • Cell death
  • Epidermis
  • HECT
  • P63
  • Skin
  • Transcription
  • Ubiquitin
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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