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Tob1通过拮抗母体β-连环蛋白的转录活性来控制斑马鱼胚胎的背侧发育。

Tob1 controls dorsal development of zebrafish embryos by antagonizing maternal beta-catenin transcriptional activity.

作者信息

Xiong Bo, Rui Yanning, Zhang Min, Shi Kehui, Jia Shunji, Tian Tian, Yin Kun, Huang Huizhe, Lin Shuyong, Zhao Xingang, Chen Yinghua, Chen Ye-Guang, Lin Sheng-Cai, Meng Anming

机构信息

State Key Laboratory of Biomembrane and Membrane Biotechnology, Protein Sciences Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.

出版信息

Dev Cell. 2006 Aug;11(2):225-38. doi: 10.1016/j.devcel.2006.06.012.

Abstract

Maternal beta-catenin and Nodal signals are essential for the formation of the dorsal organizer, which, in turn, induces neural and other dorsal tissue development in vertebrate embryos. Tob (Transducer of ErbB2) proteins possess antiproliferative properties and are known to influence BMP signaling, but their relationship to other signaling pathways and to embryonic patterning in general was unclear. In this study, we demonstrate that zebrafish tob1a is required for correct dorsoventral patterning. Mechanistically, Tob1a inhibits beta-catenin transcriptional activity by physically associating with beta-catenin and preventing the formation of beta-catenin/LEF1 complexes. Although Tob1a can also inhibit the transcriptional activity of the Nodal effector Smad3, its role in limiting dorsal development is executed primarily by antagonizing the beta-catenin signal. We further demonstrate that Tob family members across species share similar biochemical properties and biological activities.

摘要

母体β-连环蛋白和Nodal信号对于背侧组织者的形成至关重要,而背侧组织者反过来又诱导脊椎动物胚胎中的神经和其他背侧组织发育。Tob(ErbB2转导蛋白)蛋白具有抗增殖特性,并且已知会影响骨形态发生蛋白(BMP)信号传导,但它们与其他信号通路以及一般胚胎模式形成的关系尚不清楚。在本研究中,我们证明斑马鱼tob1a对于正确的背腹模式形成是必需的。从机制上讲,Tob1a通过与β-连环蛋白物理结合并阻止β-连环蛋白/淋巴样增强因子1(LEF1)复合物的形成来抑制β-连环蛋白的转录活性。虽然Tob1a也可以抑制Nodal效应器Smad3的转录活性,但其在限制背侧发育中的作用主要是通过拮抗β-连环蛋白信号来实现的。我们进一步证明,跨物种的Tob家族成员具有相似的生化特性和生物学活性。

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