p63 is upstream of IKKα in epidermal development

Eleonora Candi, Alessandro Terrinoni, Alessandro Rufini, Anissa Chikh, Anna Maria Lena, Yasuhiro Suzuki, Berna S. Sayan, Richard A. Knight, Gerry Melino

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermis, the outer layer of the skin composed of keratinocytes, develops following the action of the transcription factor p63. The mouse TrP63 gene contains two promoters, driving the production of distinct proteins, one with an N-terminal trans-activation domain (TAp63) and one without (ΔNp63), although their relative contribution to epidermal development is not clearly established. To identify the relative role of p63 isoforms in relation to IKKα, also known to be essential for epithelial development, we performed both molecular and in vivo analyses using genetic complementation in mice. We found that the action of TAp63 is mediated at the molecular level by direct and indirect transactivation of IKKα and Ets-1, respectively. We also found that ΔNp63 upregulates IKKα indirectly, through GATA-3. Our data are consistent with a role for p63 directly upstream of IKKα in epithelial development.

Original languageEnglish
Pages (from-to)4617-4622
Number of pages6
JournalJournal of Cell Science
Volume119
Issue number22
DOIs
Publication statusPublished - Nov 15 2006

Keywords

  • Cornification
  • Development
  • Differentiation
  • Epidermis
  • p63
  • Skin

ASJC Scopus subject areas

  • Cell Biology

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