TY - JOUR
T1 - FAK interaction with MBD2
T2 - A link from cell adhesion to nuclear chromatin remodeling?
AU - Mei, Lin
AU - Xiong, Wen Cheng
N1 - Funding Information:
This work is supported by NIH (National Institutes of Health) (to L.M. and W.-C. Xiong).
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - FAK
KW - MBD2
KW - Muscle differentiation
KW - Myogenin
KW - PYK2
UR - http://www.scopus.com/inward/record.url?scp=77449109109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77449109109&partnerID=8YFLogxK
U2 - 10.4161/cam.4.1.10343
DO - 10.4161/cam.4.1.10343
M3 - Comment/debate
C2 - 19949307
AN - SCOPUS:77449109109
SN - 1933-6918
VL - 4
SP - 77
EP - 80
JO - Cell Adhesion and Migration
JF - Cell Adhesion and Migration
IS - 1
ER -