Nishi K, Schnier J B, Bradbury E M
School of Medicine, University of California at Davis, Davis, California 95616, USA.
Exp Cell Res. 1998 Sep 15;243(2):222-31. doi: 10.1006/excr.1998.4166.
The staurosporine-induced G1 cell cycle arrest was analyzed in a variety of cell lines which includes human tumor cell lines and oncogene-transformed NIH3T3 cell lines. All the cell lines which were sensitive to staurosporine-induced G1 arrest contained a functional retinoblastoma protein (pRB). However, when pRB-lacking fibroblast cells derived from pRB knockout mice were tested they were also sensitive to G1 arrest by staurosporine, indicating that the inactivation of pRB alone is not sufficient for the abrogation of staurosporine-induced G1 arrest. In searching for a common event caused by staurosporine, the cyclin-dependent kinase (CDK) inhibitor protein p27kip1 but not p21cip1 was found to accumulate after staurosporine treatment in all the cell lines examined. This accumulation occurred regardless of the induction of the G1 arrest. The result indicates that the accumulation of p27kip1 is the cell's primary response to staurosporine and that the capability of staurosporine to induce G1 arrest depends on the integrity of cell cycle regulatory components which are downstream of p27kip1.
在多种细胞系中分析了星形孢菌素诱导的G1期细胞周期阻滞，这些细胞系包括人肿瘤细胞系和癌基因转化的NIH3T3细胞系。所有对星形孢菌素诱导的G1期阻滞敏感的细胞系都含有功能性视网膜母细胞瘤蛋白（pRB）。然而，当测试来自pRB基因敲除小鼠的缺乏pRB的成纤维细胞时，它们对星形孢菌素诱导的G1期阻滞也敏感，这表明仅pRB失活不足以消除星形孢菌素诱导的G1期阻滞。在寻找由星形孢菌素引起的共同事件时，发现细胞周期蛋白依赖性激酶（CDK）抑制蛋白p27kip1而非p21cip1在所有检测的细胞系中经星形孢菌素处理后会积累。这种积累与G1期阻滞的诱导无关。结果表明，p27kip1的积累是细胞对星形孢菌素的主要反应，并且星形孢菌素诱导G1期阻滞的能力取决于p27kip1下游的细胞周期调节成分的完整性。
