FAK interaction with MBD2 A link from cell adhesion to nuclear chromatin remodeling?
FAK interaction with MBD2 A link from cell adhesion to nuclear chromatin remodeling?
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DOI：
10.4161/cam.4.1.10343
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发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Xiong, Wen-Cheng
中科院分区：
文献类型：
--
作者：
Mei, Lin;Xiong, Wen-Cheng
细胞粘附、迁移、增殖和分化是紧密联系和协调的细胞过程。细胞粘附依赖性基因表达被认为有助于这种协调。粘着斑激酶（FAK）及其相关蛋白PYK 2（富含脯氨酸的酪氨酸激酶2）是细胞粘附激活的酪氨酸激酶的主要家族，在这些细胞过程中发挥重要作用。尽管FAK或PYK 2已知是一种支架蛋白，将许多细胞质蛋白募集到粘着斑复合物中并调节粘着斑转换和细胞迁移，但FAK或PYK 2如何连接到细胞核并调节基因表达仍很不清楚。我们最近报道了FAK通过与MBD 2（MethylCpG bindingdomainprotein 2）相互作用调节异染色质重塑的新信号传导，这可能是FAK调节肌细胞生成素表达和肌肉分化的基础。通过对FAK-MBD 2相互作用的分析，获得了两个见解。这种相互作用似乎是足够的，但不是必需的，为FAK易位或维持在核中。核FAK-MBD 2复合物引起异染色质组织改变，并减少MBD 2与HDAC 1（组蛋白脱乙酰酶复合物1）和肌细胞生成素启动子中甲基CpG位点的结合，从而诱导肌细胞生成素表达。这些结果证明了FAK调控基因表达的新机制，并表明细胞粘附和细胞分化之间的潜在联系。
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.