Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC(-/-) colon carcinoma
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC(-/-) colon carcinoma
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DOI：
10.1126/science.275.5307.1784
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发表时间：
1997-03-21
期刊：
影响因子：
56.9
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Korinek, V;Barker, N;Clevers, H
大肠腺瘤性息肉病（adenomatous polyposis coli，APC）肿瘤抑制蛋白与β-catenin结合，β-catenin是最近显示与Tcf和Lef转录因子相互作用的蛋白。发现APC（-/-）结肠癌细胞的细胞核含有稳定的β-连环蛋白-hTcf-4复合物，该复合物是组成型活性的，如通过Tcf报告基因的转录所测量的。APC的重新引入使β-catenin从hTcf-4中去除，并取消转录反式激活。APC功能的丧失导致的Tcf靶基因的组成性转录可能是结肠上皮早期转化的关键事件。
The adenomatous polyposis coli (APC) tumor suppressor protein binds to beta-catenin, a protein recently shown to interact with Tcf and Lef transcription factors, The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium, was cloned and characterized, hTcf-4 transactivates transcription only when associated with beta-catenin. Nuclei of APC(-/-) colon carcinoma cells were found to contain a stable beta-catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed beta-catenin from hTcf-4 and abrogated the transcriptional transactivation, Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.