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


ABSTRACT: 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.

SUBMITTER: Gebhardt A 

PROVIDER: S-EPMC2063541 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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

Gebhardt Anneli A   Frye Michaela M   Herold Steffi S   Benitah Salvador Aznar SA   Braun Kristin K   Samans Birgit B   Watt Fiona M FM   Elsässer Hans-Peter HP   Eilers Martin M  

The Journal of cell biology 20060101 1


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 keratino  ...[more]

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