YAP 和 ROCK2 之间底物刚性依赖性正反馈调节。
Substrate rigidity-dependent positive feedback regulation between YAP and ROCK2.
机构信息
a Frontiers of Innovative Research in Science and Technology , Konan University , Kobe, Hyogo , Japan.
b Laboratory for Comprehensive Bioimaging , Riken Qbic , Osaka , Japan.
出版信息
Cell Adh Migr. 2018 Mar 4;12(2):101-108. doi: 10.1080/19336918.2017.1338233. Epub 2018 Jan 29.
Extracellular matrix (ECM) stiffness influences gene expression, leading to modulation of various cellular functions. While ROCK2 regulates actomyosin activity as well as cell migration and proliferation, expression of ROCK2 is increased in response to stiffening ECM. However, the mechanism underlying rigidity-dependent ROCK2 expression remains elusive. Here, we show that YAP, a mechanically regulated transcription coactivator, upregulates ROCK2 expression in an ECM rigidity-dependent manner. YAP interacted with the ROCK2 promoter region in an actomyosin activity-dependent manner. Knockdown of YAP decreased ROCK2 expression while activity of the ROCK2 promoter was upregulated by expressing constitutively active YAP. Furthermore, we found that ROCK2 expression promotes transcriptional activation by YAP. Our results reveal a novel positive feedback loop between YAP and ROCK2, which is modulated by ECM stiffness.
细胞外基质（ECM）硬度会影响基因表达，从而调节各种细胞功能。ROCK2 调节肌动球蛋白活性以及细胞迁移和增殖，而 ROCK2 的表达会在 ECM 变硬时增加。然而，刚性依赖的 ROCK2 表达的机制仍然难以捉摸。在这里，我们表明 YAP，一种机械调节转录共激活因子，以 ECM 刚性依赖的方式上调 ROCK2 的表达。YAP 以肌动球蛋白活性依赖的方式与 ROCK2 启动子区域相互作用。YAP 的敲低会降低 ROCK2 的表达，而表达组成性激活的 YAP 会上调 ROCK2 启动子的活性。此外，我们发现 ROCK2 的表达促进了 YAP 的转录激活。我们的结果揭示了 YAP 和 ROCK2 之间的一种新的正反馈环，该环受 ECM 硬度的调节。
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