The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase.
The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase.
复制标题
抑癌基因产物 APC 阻断细胞周期从 G0/G1 期进展至 S 期。
作者：
G. Baeg;Akihiko Matsumine;Tadahiro Kuroda;R. Bhattacharjee;I. Miyashiro;K. Toyoshima;T. Akiyama
APC基因在家族性腺瘤性息肉病（FAP）以及散发性结直肠肿瘤中发生突变。APC基因的产物是一个300 kDa的细胞质蛋白，与粘附连接蛋白catenin相关。本研究表明，APC的过表达阻断了血清诱导的细胞周期从G0/G1期向S期的进展。在FAP和/或结直肠肿瘤中发现的突变APC的抑制作用较弱，部分阻碍了正常APC的活性。过表达cyclin E/CDK2或cyclin D1/CDK4可减轻APC的细胞周期阻断活性。与此结果一致的是，在过表达APC的细胞中，CDK2的激酶活性显著下调，但其合成保持不变，而CDK4的活性几乎没有受到影响。这些结果表明，APC可能通过负向调节细胞周期蛋白- CDK复合物的活性来调节细胞周期。
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 G0/G1 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.
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DOI：
10.1073/pnas.90.23.11109
发表时间：
1993-12-01
影响因子：
11.1
作者：
JOSLYN, G;RICHARDSON, DS;ALBER, T
通讯作者：
ALBER, T
影响因子：
56.9
作者：
LEPPERT, M;DOBBS, M;WHITE, R
通讯作者：
WHITE, R
DOI：
10.1073/pnas.91.19.8969
发表时间：
1994-09-13
影响因子：
11.1
作者：
FODDE, R;EDELMANN, W;KUCHERLAPATI, R
通讯作者：
KUCHERLAPATI, R
影响因子：
3.7
作者：
NODA, A;NING, Y;SMITH, JR
通讯作者：
SMITH, JR
野生型和突变型 APC 基因产物之间的关联。
影响因子：
11.2
作者：
Su,LK;Johnson,KA;Smith,KJ;Hill,DE;Vogelstein,B;Kinzler,KW
通讯作者：
Kinzler,KW