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First published online November 8, 2006

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p63 and IKK: a skin-deep pathway

The epidermis – the skin's outer layer – is a stratified epithelium that provides the body with an essential waterproof and bug-proof covering. Its development requires the activity of the p53-related transcription factor p63 and IB kinase (IKK) – a kinase that regulates the transcription factor NF-B but also has kinase-independent activities. On p. 4617, Eleonora Candi, Gerry Melino and co-authors report that p63 acts upstream of IKK in epidermis formation. p63 exists as two major isoforms: TAp63, which contains an N-terminal transactivation domain; and Np63, which lacks this domain. The authors show that TAp63 (but not Np63) directly induces IKK expression by targeting p53-like responsive elements in the IKK promoter. They also show that p63 drives IKK expression indirectly by regulating the expression of two other transcription factors that bind to the IKK promoter: Tap63 drives Ets-1 expression and both isoforms drive GATA-3 expression. Finally, the authors show that genetic complementation with TAp63 and Np63 rescues IKK expression in p63^–/– mice This demonstration that p63 acts upstream of IKK in epithelial development may have clinical implications – for example, in the treatment of severe burns.

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p63 is upstream of IKK in epidermal development

Eleonora Candi, Alessandro Terrinoni, Alessandro Rufini, Anissa Chikh, Anna Maria Lena, Yasuhiro Suzuki, Berna S. Sayan, Richard A. Knight, and Gerry Melino
JCS 2006 119: 4617-4622. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?