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. |