Koff A, Ohtsuki M, Polyak K, Roberts J M, Massagué J
Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Science. 1993 Apr 23;260(5107):536-9. doi: 10.1126/science.8475385.
Transforming growth factor-beta (TGF-beta) is a naturally occurring growth inhibitory polypeptide that arrests the cell cycle in middle to late G1 phase. Cells treated with TGF-beta contained normal amounts of cyclin E and cyclin-dependent protein kinase 2 (Cdk2) but failed to stably assemble cyclin E-Cdk2 complexes or accumulate cyclin E-associated kinase activity. Moreover, G1 phase extracts from TGF-beta-treated cells did not support activation of endogenous cyclin-dependent protein kinases by exogenous cyclins. These effects of TGF-beta, which correlated with the inhibition of retinoblastoma protein phosphorylation, suggest that mammalian G1 cyclin-dependent kinases, like their counterparts in yeast, are targets for negative regulators of the cell cycle.
转化生长因子-β（TGF-β）是一种天然存在的生长抑制性多肽，它能使细胞周期停滞在G1期的中晚期。用TGF-β处理的细胞含有正常量的细胞周期蛋白E和细胞周期蛋白依赖性蛋白激酶2（Cdk2），但未能稳定组装细胞周期蛋白E-Cdk2复合物或积累细胞周期蛋白E相关的激酶活性。此外，来自TGF-β处理细胞的G1期提取物不支持外源性细胞周期蛋白对内源性细胞周期蛋白依赖性蛋白激酶的激活。TGF-β的这些作用与视网膜母细胞瘤蛋白磷酸化的抑制相关，表明哺乳动物G1期细胞周期蛋白依赖性激酶与其在酵母中的对应物一样，是细胞周期负调控因子的作用靶点。
