FAK interaction with MBD2: A link from cell adhesion to nuclear chromatin remodeling?
Cell adhesion, migration, proliferation and differentiation are tightly linked and coordinated cellular processes. Cell adhesion dependent gene expression is believed to contribute to such coordination. Focal adhesion kinase (FAK) and its related protein, PYK2 (proline rich tyrosine kinase 2), are a major family of cell adhesion activated tyrosine kinases that play important roles in these cellular processes. Whereas FAK or PYK2 is known to be a scaffold protein, recruiting many cytoplasmic proteins into the focal adhesion complex and regulating focal adhesion turnover and cell migration, how FAK or PYK2 links to the nuclei and regulates gene expression remain largely unclear. We recently report a new signaling of FAK in regulating heterochromatin remodeling by its interaction with MBD2 (Methyl CpG binding domain protein 2), which may underlie FAK regulation of myogenin expression and muscle differentiation. Two insights have been obtained through the analysis of FAK-MBD2 interaction. The interaction appears to be sufficient, but not necessary, for FAK translocation into or maintaining in the nucleus. The nuclear FAK-MBD2 complexes cause altered heterochromatin organization and decreased MBD2 association with HDAC1 (histone deacetylase complex 1) and methyl CpG site in the myogenin promoter, thus, inducing myogenin expression. These results demonstrate a new mechanism underlying FAK regulation of gene expression, and suggest a potential link between cell adhesion and cell differentiation.
Mei
Lin
L
Institute of Molecular Medicine & Genetics and Department of Neurology, Medical College of Georgia, Augusta, GA, USA.
Xiong
Wen-Cheng
WC
D000818:Animals; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding
D004268:DNA-Binding Proteins; C115368:MBD2 protein; D051416:Focal Adhesion Protein-Tyrosine Kinases