کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1931205 | 1050544 | 2010 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Skn-1a/Oct-11 and ΔNp63α exert antagonizing effects on human keratin expression Skn-1a/Oct-11 and ΔNp63α exert antagonizing effects on human keratin expression](/preview/png/1931205.png)
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.
Research highlights
► Skn-1a markedly downregulates ΔNp63-driven K14 expression.
► ΔNp63 inhibits Skn-1a-mediated K10 expression.
► ΔNp63, mutated in SAM domain, is less effecting in K10 downregulation.
► Immunolocalization in human skin of the two transcription factors is partially overlapping.
► The antagonistic effects of Skn-1a and p63 is through competition for overlapping responsive elements or through an indirect interaction.
Journal: Biochemical and Biophysical Research Communications - Volume 401, Issue 4, 29 October 2010, Pages 568–573