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First published online November 8, 2006

Journal of Cell Science 119, 2203e (2006)
© The Company of Biologists Limited
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In this issue

p63 and IKK{alpha}: a skin-deep pathway


Figure 1

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 I{kappa}B kinase {alpha} (IKK{alpha}) – a kinase that regulates the transcription factor NF-{kappa}B but also has kinase-independent activities. On p. 4617, Eleonora Candi, Gerry Melino and co-authors report that p63 acts upstream of IKK{alpha} in epidermis formation. p63 exists as two major isoforms: TAp63, which contains an N-terminal transactivation domain; and {Delta}Np63, which lacks this domain. The authors show that TAp63 (but not {Delta}Np63) directly induces IKK{alpha} expression by targeting p53-like responsive elements in the IKK{alpha} promoter. They also show that p63 drives IKK{alpha} expression indirectly by regulating the expression of two other transcription factors that bind to the IKK{alpha} promoter: Tap63 drives Ets-1 expression and both isoforms drive GATA-3 expression. Finally, the authors show that genetic complementation with TAp63 and {Delta}Np63 rescues IKK{alpha} expression in p63–/– mice This demonstration that p63 acts upstream of IKK{alpha} in epithelial development may have clinical implications – for example, in the treatment of severe burns.


Related articles in JCS:

p63 is upstream of IKK{alpha} 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
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