Published 3 January 2006. doi:10.1083/jcb.200506057
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 1, 139-149
Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1
Anneli Gebhardt1,
Michaela Frye3,
Steffi Herold2,
Salvador Aznar Benitah3,
Kristin Braun3,
Birgit Samans2,
Fiona M. Watt3,
Hans-Peter Elsässer1, and
Martin Eilers2
1 Institute for Cell Biology, University of Marburg, 35033 Marburg, Germany
2 Institute for Molecular Biology and Tumor Research, University of Marburg, 35033 Marburg, Germany
3 Cancer Research UK London Research Institute, London WC2A 3PX, England, UK
Correspondence to Martin Eilers: eilers{at}imt.uni-marburg.de
Myc plays a key role in homeostasis of the skin. We show that Miz1, which mediates Myc repression of gene expression, is expressed in the epidermal basal layer. A large percentage of genes regulated by the MycMiz1 complex in keratinocytes encode proteins involved in cell adhesion, and some, including the
6 and ß1 integrins, are directly bound by Myc and Miz1 in vivo. Using a Myc mutant deficient in Miz1 binding (MycV394D), we show that Miz1 is required for the effects of Myc on keratinocyte responsiveness to TGF-ß. Myc, but not MycV394D, decreases keratinocyte adhesion and spreading. In reconstituted epidermis, Myc induces differentiation and loss of cell polarization in a Miz1-dependent manner. In vivo, overexpression of ß1 integrins restores basal layer polarity and prevents Myc-induced premature differentiation. Our data show that regulation of cell adhesion is a major function of the MycMiz1 complex and suggest that it may contribute to Myc-induced exit from the epidermal stem cell compartment.
A. Gebhardt and M. Frye contributed equally to this paper.
Abbreviations used in this paper: 4-OHT, 4-hydroxy-tamoxifen; cDNA, complementary DNA; ChIP, chromatin immunoprecipitation; DED, de-epidermized dermis.

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