p63 is upstream of IKKα in epidermal development
Author:
Candi Eleonora1, Terrinoni Alessandro1, Rufini Alessandro1, Chikh Anissa1, Lena Anna Maria1, Suzuki Yasuhiro2, Sayan Berna S.3, Knight Richard A.3, Melino Gerry123
Affiliation:
1. Biochemistry Laboratory, IDI-IRCCS, c/o University of Rome `Tor Vergata', 00133 Rome, Italy 2. Fondazione S. Lucia, via Ardeatina, 00179 Rome, Italy 3. Medical Research Council, Toxicology Unit, Leicester University, Leicester, LE1 9HN, UK
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.
Publisher
The Company of Biologists
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