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Publication : Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1.

First Author  Gebhardt A Year  2006
Journal  J Cell Biol Volume  172
Issue  1 Pages  139-49
PubMed ID  16391002 Mgi Jnum  J:104402
Mgi Id  MGI:3611943 Doi  10.1083/jcb.200506057
Citation  Gebhardt A, et al. (2006) Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1. J Cell Biol 172(1):139-49
abstractText  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 Myc-Miz1 complex in keratinocytes encode proteins involved in cell adhesion, and some, including the alpha6 and beta1 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-beta. 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 beta1 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 Myc-Miz1 complex and suggest that it may contribute to Myc-induced exit from the epidermal stem cell compartment.
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