TY - JOUR
T1 - Skn-1a/Oct-11 and ΔNp63α exert antagonizing effects on human keratin expression
AU - Lena, Anna Maria
AU - Cipollone, Rita
AU - Amelio, Ivano
AU - Catani, Maria Valeria
AU - Ramadan, Safaa
AU - Browne, Gareth
AU - Melino, Gerry
AU - Candi, Eleonora
PY - 2010/10/29
Y1 - 2010/10/29
N2 - 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.
AB - 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.
KW - Differentiation
KW - Epidermal stratification
KW - P63
KW - POU domain protein
KW - Skn-1a
UR - http://www.scopus.com/inward/record.url?scp=77958479635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958479635&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2010.09.102
DO - 10.1016/j.bbrc.2010.09.102
M3 - Article
C2 - 20888799
AN - SCOPUS:77958479635
VL - 401
SP - 568
EP - 573
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -