Dependence of cyclin E-CDK2 kinase activity on cell anchorage
Dependence of cyclin E-CDK2 kinase activity on cell anchorage
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DOI：
10.1126/science.271.5248.499
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发表时间：
1996-01-26
期刊：
影响因子：
56.9
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
--
作者：
Fang, F;Orend, G;Ruoslahti, E
大多数非恶性细胞是锚定依赖性的；它们需要附着在基质上才能生长，在某些情况下，还需要生存。这个要求在致癌转化中丢失了。细胞周期的G(1)-S转变所必需的周期蛋白E-CDK2复合物在附着的人成纤维细胞的G(1)期晚期被激活，但在维持悬浮状态的成纤维细胞中没有被激活。在转化成纤维细胞中，无论附着与否，该复合物都具有活性。悬浮细胞中缺乏细胞周期蛋白E-CDK2活性似乎是由于CDK2抑制剂的表达增加和伴随的苏氨酸-160上CDK2磷酸化的降低。细胞周期蛋白E-CDK2活性的抑制可能是细胞生长的锚定依赖性的基础。
Most nonmalignant cells are anchorage-dependent; they require substrate attachment for growth and, in some instances, survival. This requirement is lost on oncogenic transformation. The cyclin E-CDK2 complex, which is required for the G(1)-S transition of the cell cycle, was activated in late G(1) phase in attached human fibroblasts, but not in fibroblasts maintained in suspension. In transformed fibroblasts the complex was active regardless of attachment, The lack of cyclin E-CDK2 activity in suspended cells appeared to result from increased expression of CDK2 inhibitors and a concomitant decrease in phosphorylation of CDK2 on threonine-160. Suppression of cyclin E-CDK2 activity may thus underlie the anchorage dependence of cell growth.