A yeast model system for functional analysis of beta-catenin signaling.
A yeast model system for functional analysis of beta-catenin signaling.
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DOI：
10.1083/jcb.200204063
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发表时间：
2002-09-16
期刊：
影响因子：
--
通讯作者：
Papkoff J
中科院分区：
文献类型：
--
作者：
Lee MS;D'Amour KA;Papkoff J
我们开发了一个新的酿酒酵母模型系统来研究β-catenin（β-cat）信号转导的分子事件。哺乳动物β-cat与TCF 4或LEF 1的共表达导致这些蛋白质和功能复合物的核积累，该功能复合物激活来自含有白细胞增强因子（LEF）/T细胞因子（TCF）反应元件的构建体的报告基因转录。报告基因转录是组成型的，需要β-cat和TCF 4或LEF 1的表达，并且不受突变的LEF/TCF结合元件或TCF 4或LEF 1突变体的支持。E-钙粘蛋白的胞质结构域或腺瘤性结肠息肉病（APC）蛋白（APC-25）的功能片段与β-cat复合，减少β-cat与TCF 4的结合，并导致β-cat的胞质定位增加和报告基因激活减少。APC-25中推定的核输出信号序列的系统性突变降低APC-25与β-cat的结合并恢复报告基因转录。其他β-cat信号传导组分Axin和糖原合成酶激酶3β形成类似于哺乳动物细胞中发现的多亚基复合物。F-box蛋白β-transducin repeat蛋白的共表达降低了β-cat的稳定性并降低了报告基因的激活。因此，我们已经在酵母中重建了功能性β-cat信号转导途径，并表明β-cat信号转导可以在多个水平上进行调节，包括蛋白质亚细胞定位，蛋白质复合物形成和蛋白质稳定性。
We have developed a novel Saccharomyces cerevisiae model system to dissect the molecular events of β-catenin (β-cat) signaling. Coexpression of mammalian β-cat with TCF4 or LEF1 results in nuclear accumulation of these proteins and a functional complex that activates reporter gene transcription from constructs containing leukocyte enhancer factor (LEF)/T cell factor (TCF) response elements. Reporter transcription is constitutive, requires expression of both β-cat and TCF4 or LEF1, and is not supported by mutated LEF/TCF binding elements or by TCF4 or LEF1 mutants. A cytoplasmic domain of E-cadherin or a functional fragment of adenomatous polyposis coli (APC) protein (APC-25) complexes with β-cat, reduces β-cat binding to TCF4, and leads to increased cytoplasmic localization of β-cat and a reduction in reporter activation. Systematic mutation of putative nuclear export signal sequences in APC-25 decreases APC-25 binding to β-cat and restores reporter gene transcription. Additional β-cat signaling components, Axin and glycogen synthase kinase 3β, form a multisubunit complex similar to that found in mammalian cells. Coexpression of the F-box protein β-transducin repeat-containing protein reduces the stability of β-cat and decreases reporter activation. Thus, we have reconstituted a functional β-cat signal transduction pathway in yeast and show that β-cat signaling can be regulated at multiple levels, including protein subcellular localization, protein complex formation, and protein stability.
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影响因子：
7.8
作者：
Hinck, L;Nelson, W J;Papkoff, J
通讯作者：
Papkoff, J
DOI：
10.1083/jcb.123.6.1857
发表时间：
1993-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bradley RS;Cowin P;Brown AM
通讯作者：
Brown AM
DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
Gumbiner BM
影响因子：
9.2
作者：
Hart, MJ;de los Santos, R;Polakis, P
通讯作者：
Polakis, P
影响因子：
11.4
作者：
GIESE, K;GROSSCHEDL, R
通讯作者：
GROSSCHEDL, R