Pu Zhongyue, Wang Yongshun, Liu Xinxin, Liu Jingjin, Cui Jinjin, Wang Yan, Lv Bo, Yu Bo
Department of Cardiology, 2nd Affiliated Hospital, and Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, China.
J Vasc Res. 2017;54(1):13-21. doi: 10.1159/000452409. Epub 2017 Jan 25.
Cables1 (Cdk5 and Abl enzyme substrate 1) is a vital cell cycle regulator and a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Here, we report on the critical role of the Cables1/p21 pathway, which inhibits cell proliferation and induces cell senescence in human umbilical vein endothelial cells. Moreover, we confirmed that silencing of Cables1 promoted cell proliferation as well as increased resistance to angiotensin II-induced senescence, at least in part, by altering Cables1 activation. We further demonstrated that knockdown of p21 reverses Cables1-mediated cell growth inhibition and cell senescence. Taken together, these results suggest that the Cables1/p21 pathway has a strong effect on the induction of cell senescence and inhibition of cell growth, and acts as a novel regulatory mechanism in which p21 is probably one of several downstream effector molecules to mediate Cables1.
Cables1（细胞周期蛋白依赖性激酶5和Abl酶底物1）是一种重要的细胞周期调节因子，也是一种候选肿瘤抑制因子，它通过抑制细胞周期蛋白依赖性激酶来负向调节细胞生长。在此，我们报道了Cables1/p21信号通路在人脐静脉内皮细胞中抑制细胞增殖并诱导细胞衰老的关键作用。此外，我们证实，至少部分通过改变Cables1的激活，沉默Cables1可促进细胞增殖并增强对血管紧张素II诱导的衰老的抗性。我们进一步证明，敲低p21可逆转Cables1介导的细胞生长抑制和细胞衰老。综上所述，这些结果表明，Cables1/p21信号通路对细胞衰老的诱导和细胞生长的抑制具有强烈作用，并作为一种新的调节机制，其中p21可能是介导Cables1的几个下游效应分子之一。
