Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27Kip1
Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27Kip1
复制标题
DOI：
10.1172/jci5461
复制
发表时间：
1999-03-01
影响因子：
15.9
通讯作者：
Shankland, SJ
中科院分区：
文献类型：
--
作者：
Hiromura, K;Pippin, JW;Shankland, SJ
增殖和凋亡在许多类型的炎性疾病中增加。细胞周期蛋白激酶抑制剂p27（Kip 1）（p27）在限制增殖中的作用已被证明。在这项研究中，我们发现，p27（-/-）肾小球系膜细胞和成纤维细胞的凋亡率显着升高，而不是增殖，当剥夺生长因子。通过恢复p27表达来挽救细胞凋亡。细胞周期蛋白A依赖性激酶2（CDK 2）的活性，但不是细胞周期蛋白E-CDK 2的活性，增加了血清饥饿的p27-/-细胞，并降低CDK 2的活性，无论是cardiac（Roscovitine）或显性负突变体，抑制细胞凋亡，我们的研究结果表明，一个新的生物学功能的CDK抑制剂p27是通过抑制CDK 2活性的细胞凋亡的保护。这些结果表明，CDK抑制剂是必要的协调细胞周期和细胞死亡程序，使细胞活力保持在退出细胞周期。
Proliferation and apoptosis are increased in many types of inflammatory diseases. A role for the cyclin kinase inhibitor p27(Kip1) (p27) in limiting proliferation has been shown. In this study, we show that p27(-/-) mesangial cells and fibroblasts have strikingly elevated rates of apoptosis, not proliferation, when deprived of growth factors. Apoptosis was rescued by restoration of p27 expression. Cyclin A-cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E-CDK2 activity, was increased in serum-starved p27-/- cells, and decreasing CDK2 activity, either pharmacologically (Roscovitine) or by a dominant-negative mutant, inhibited apoptosis, Our results show that a new biological function for the CDK inhibitor p27 is protection of cells from apoptosis by constraining CDK2 activity. These results suggest that CDK inhibitors are necessary for coordinating the cell cycle and cell-death programs so that cell viability is maintained during exit from the cell cycle.