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First published online November 8, 2006
doi: 10.1242/10.1242/jcs.03265

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p63 is upstream of IKK in epidermal development

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

^* Authors for correspondence (e-mail: candi{at}uniroma2.it; gm89{at}le.ac.uk)

Accepted 19 September 2006

Summary

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 (Np63), although their relative contribution to epidermal development is not clearly established. To identify the relative role of p63 isoforms in relation to IKK, 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 IKK and Ets-1, respectively. We also found that Np63 upregulates IKK indirectly, through GATA-3. Our data are consistent with a role for p63 directly upstream of IKK in epithelial development.

Key words: p63, Epidermis, Cornification, Skin, Differentiation, Development

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p63 and IKK: a skin-deep pathway

JCS 2006 119: 2203. [Full Text]  

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