Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1
| Autor: | Fiona M. Watt, Salvador Aznar Benitah, Steffi Herold, Michaela Frye, Martin Eilers, Birgit Samans, Kristin M. Braun, Anneli Gebhardt, Hans-Peter Elsässer |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Keratinocytes
Ubiquitin-Protein Ligases Cellular differentiation Integrin Genes myc Article Proto-Oncogene Proteins c-myc Mice Cell Movement Transforming Growth Factor beta Cell polarity Cell Adhesion medicine Animals Humans Nuclear protein Cell adhesion Research Articles Epidermis (botany) biology Integrin beta1 Cell Polarity Nuclear Proteins Cell Differentiation Cell Biology Transforming growth factor beta Protein Inhibitors of Activated STAT Molecular biology Cell biology medicine.anatomical_structure Multiprotein Complexes biology.protein Keratinocyte |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | 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 α6 and β1 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-β. 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 β1 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. |
| Databáze: | OpenAIRE |
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