THE TUMOR-SUPPRESSOR GENE-PRODUCT APC BLOCKS CELL-CYCLE PROGRESSION FROM G(0)/G(1) TO S-PHASE
THE TUMOR-SUPPRESSOR GENE-PRODUCT APC BLOCKS CELL-CYCLE PROGRESSION FROM G(0)/G(1) TO S-PHASE
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DOI：
10.1002/j.1460-2075.1995.tb00249.x
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发表时间：
1995-11-15
期刊：
影响因子：
11.4
通讯作者：
AKIYAMA, T
中科院分区：
文献类型：
--
作者：
BAEG, GH;MATSUMINE, A;AKIYAMA, T
APC基因在家族性腺瘤性息肉病（FAP）和散发性结直肠肿瘤中发生突变，APC基因的产物是一种与粘附连接蛋白连环蛋白相关的300 kDa胞质蛋白。在此，我们发现APC的过度表达阻断了血清诱导的细胞周期从G（0）G（1）期到S期的进程。在FAP和/或结直肠肿瘤中鉴定的突变APC的抑制性较低，并且部分地阻断正常APC的活性。APC的细胞周期阻断活性通过cyclin E/CDK 2或cyclin D1/CDK 4的过表达而减轻。与此结果一致，CDK 2的激酶活性在过表达APC的细胞中显著下调，尽管其合成保持不变，而CDK 4活性几乎不受影响。这些结果表明，APC可能通过负性调节细胞周期蛋白-CDK复合物的活性在细胞周期的调节中发挥作用。
The APC gene is mutated in familial adenomatous polyposis (FAP) as well as in sporadic colorectal tumours, The product of the APC gene is a 300 kDa cytoplasmic protein associated with the adherence junction protein catenin, Here we show that overexpression of APC blocks serum-induced cell cycle progression from G(0)G(1) to the S phase. Mutant APCs identified in FAP and/or colorectal tumours were less inhibitory and partially obstructed the activity of the normal APC, The cell-cycle blocking activity of APC was alleviated by the overexpression of cyclin E/CDK2 or cyclin D1/CDK4. Consistent with this result, kinase activity of CDK2 was significantly down-regulated in cells overexpressing APC although its synthesis remained unchanged, while CDK4 activity was barely affected. These results suggest that APC may play a role in the regulation of the cell cycle by negatively modulating the activity of cyclin-CDK complexes.