Skn-1a/Oct-11 and ΔNp63α exert antagonizing effects on human keratin expression.
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.
Lena
Anna Maria
AM
Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", 00133 Rome, Italy.
Cipollone
Rita
R
Amelio
Ivano
I
Catani
Maria Valeria
MV
Ramadan
Safaa
S
Browne
Gareth
G
Melino
Gerry
G
Candi
Eleonora
E
D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D053550:Keratin-10 / Q000037:antagonists & inhibitors / Q000235:genetics; D053547:Keratin-14 / Q000037:antagonists & inhibitors / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D007633:Keratins / Q000037:antagonists & inhibitors / Q000235:genetics*; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D053547:Keratin-14; D050810:Octamer Transcription Factors; C484169:POU2F3 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D053550:Keratin-10; D007633:Keratins