REGULATION OF INTRACELLULAR BETA-CATENIN LEVELS BY THE ADENOMATOUS POLYPOSIS-COLI (APC) TUMOR-SUPPRESSOR PROTEIN
REGULATION OF INTRACELLULAR BETA-CATENIN LEVELS BY THE ADENOMATOUS POLYPOSIS-COLI (APC) TUMOR-SUPPRESSOR PROTEIN
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DOI：
10.1073/pnas.92.7.3046
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
POLAKIS, P
中科院分区：
文献类型：
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作者：
MUNEMITSU, S;ALBERT, I;POLAKIS, P
APC肿瘤抑制蛋白与β-连环蛋白相关联，β-连环蛋白是一种细胞黏附蛋白，可被WNT1癌基因上调。我们研究了外源性APC表达对仅含突变型APC的结直肠癌细胞中β-连环蛋白的分布和数量的影响。野生型APC的表达通过消除SW480结直肠癌细胞系中固有的过量细胞质β-连环蛋白供应，导致总β-连环蛋白水平显著降低。这种降低是由于β-连环蛋白降解速率提高。与癌症相关的特征性截短突变型APC蛋白缺乏这种活性。突变分析表明，APC蛋白的中心区域（在肿瘤中通常缺失或严重截短）负责β-连环蛋白的下调。这些结果表明，突变型APC的肿瘤抑制活性可能因其调节β-连环蛋白能力的缺陷而受损。
The APC tumor-suppressor protein associates with beta-catenin, a cell adhesion protein that is upregulated by the WNT1 oncogene, We examined the effects of esogenous APC expression on the distribution and amount of beta-catenin in a colorectal cancer cell containing only mutant APC. Expression of wild-type APC caused a pronounced reduction in total beta-catenin levels by eliminating an excessive supply of cytoplasmic beta-catenin indigenous to the SW480 colorectal cancer cell line. This reduction was due to an enhanced rate of beta-catenin protein degradation. Truncated mutant APC proteins, characteristic of those associated with cancer, lacked this activity. Mutational analysis revealed that the central region of the APC protein, which is typically deleted or severely truncated in tumors, was responsible for the down-regulation of beta-catenin. These results suggest that the tumor-suppressor activity of mutant APC map be compromised due to a defect in its ability to regulate beta-catenin.