Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, England, UK.
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, England, UK
J Cell Biol. 2018 Sep 3;217(9):3203-3218. doi: 10.1083/jcb.201802088. Epub 2018 Jun 21.
In most tissues, anchorage-dependent growth and cell cycle progression are dependent on cells engaging extracellular matrices (ECMs) via integrin-receptor adhesion complexes. In a highly conserved manner, cells disassemble adhesion complexes, round up, and retract from their surroundings before division, suggestive of a primordial link between the cell cycle machinery and the regulation of cell adhesion to the ECM. In this study, we demonstrate that cyclin-dependent kinase 1 (CDK1) mediates this link. CDK1, in complex with cyclin A2, promotes adhesion complex and actin cytoskeleton organization during interphase and mediates a large increase in adhesion complex area as cells transition from G1 into S. Adhesion complex area decreases in G2, and disassembly occurs several hours before mitosis. This loss requires elevated cyclin B1 levels and is caused by inhibitory phosphorylation of CDK1-cyclin complexes. The inactivation of CDK1 is therefore the trigger that initiates remodeling of adhesion complexes and the actin cytoskeleton in preparation for rapid entry into mitosis.
在大多数组织中，锚定依赖性生长和细胞周期进程依赖于细胞通过整合素受体粘附复合物与细胞外基质 (ECM) 相互作用。以高度保守的方式，细胞在分裂前会解体粘附复合物、变圆并从周围环境中缩回，这表明细胞周期机制与细胞粘附到 ECM 的调节之间存在原始联系。在这项研究中，我们证明了细胞周期蛋白依赖性激酶 1 (CDK1) 介导了这种联系。CDK1 与细胞周期蛋白 A2 形成复合物，在细胞周期的间期中促进粘附复合物和肌动球蛋白细胞骨架的组织，并在细胞从 G1 进入 S 期时介导粘附复合物面积的大幅增加。在 G2 中，粘附复合物的面积减小，并且在有丝分裂前几个小时就会发生解体。这种丧失需要升高的细胞周期蛋白 B1 水平，并由 CDK1-细胞周期蛋白复合物的抑制性磷酸化引起。因此，CDK1 的失活是引发粘附复合物和肌动球蛋白细胞骨架重塑以准备快速进入有丝分裂的触发因素。
