Skn-1a/Oct-11 and ΔNp63α exert antagonizing effects on human keratin expression

Anna Maria Lena, Rita Cipollone, Ivano Amelio, Maria Valeria Catani, Safaa Ramadan, Gareth Browne, Gerry Melino, Eleonora Candi

Research output: Contribution to journalArticlepeer-review

Abstract

The formation of a stratified epidermis requires a carefully controlled balance between keratinocyte proliferation and differentiation. Here, we report the reciprocal effect on keratin expression of ΔNp63, pivotal in normal epidermal morphogenesis and maintenance, and Skn-1a/Oct-11, a POU transcription factor that triggers and regulates the differentiation of keratinocytes. The expression of Skn-1a markedly downregulated ΔNp63-driven K14 expression in luciferase reporter assays. The extent of downregulation was comparable to the inhibition of Skn-1a-mediated K10 expression upon expression of ΔNp63 ΔNp63, mutated in the protein-protein interaction domain (SAM domain; mutated in human ectodermal dysplasia syndrome), was significantly less effecting in downregulating K10, raising the possibility of a direct interaction among Skn-1a and ΔNp63. Immunolocalization in human skin biopsies revealed that the expression of the two transcription factors is partially overlapping. Co-immunoprecipitation experiments did not, however, demonstrate a direct interaction between ΔNp63 and Skn-1a, suggesting that the antagonistic effects of Skn-1a and p63 on keratin promoter transactivation is probably through competition for overlapping binding sites on target gene promoter or through an indirect interaction.

Original languageEnglish
Pages (from-to)568-573
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume401
Issue number4
DOIs
Publication statusPublished - Oct 29 2010

Keywords

  • Differentiation
  • Epidermal stratification
  • P63
  • POU domain protein
  • Skn-1a

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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