KS215 Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre Kharghar Node, Navi, Mumbai, India.
Cell Cycle. 2011 Mar 1;10(5):776-82. doi: 10.4161/cc.10.5.14954.
The activity of the dual specificity phosphatase cdc25C is required for mitotic progression though the mechanisms by which cdc25C is activated prior to mitosis in human cells remain unclear. The data presented herein show that the actin binding protein Filamin A forms a complex with cdc25C in vivo and binds preferentially to the mitotic form of cdc25C. Co-expression of Filamin A with cdc25C results in an increase in PCC induced by cdc25C, while knocking down Filamin A expression reduces the levels of PCC induced by cdc25C overexpression. Further, only a Filamin A fragment that forms a complex with both cdc25C and cyclin B1 and retains the dimerization domain can stimulate the ability of cdc25C to induce PCC. These results suggest that Filamin A provides a platform for the assembly of the cyclin B1-cdk1- cdc25C complex resulting in cdk1 activation and mitotic progression.
双重特异性磷酸酶 cdc25C 的活性对于有丝分裂的进展是必需的，尽管在人类细胞中 cdc25C 在有丝分裂之前被激活的机制尚不清楚。本文提供的资料显示，肌动蛋白结合蛋白 Filamin A 在体内与 cdc25C 形成复合物，并优先结合于有丝分裂形式的 cdc25C。Filamin A 与 cdc25C 的共表达导致 cdc25C 诱导的 PCC 增加，而敲低 Filamin A 的表达则降低了 cdc25C 过表达诱导的 PCC 水平。此外，只有形成与 cdc25C 和细胞周期蛋白 B1 复合物并保留二聚化结构域的 Filamin A 片段才能刺激 cdc25C 诱导 PCC 的能力。这些结果表明，Filamin A 为 cyclin B1-cdk1-cdc25C 复合物的组装提供了一个平台，导致 cdk1 的激活和有丝分裂的进展。
