Chibby, a nuclear β-catenin-associated antagonist of the Wnt/Wingless pathway

Ken-Ichi Takemaru; Shinji Yamaguchi; Young Sik Lee; Yang Zhang; Richard W. Carthew; Randall T. Moon

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Chibby, a nuclear β-catenin-associated antagonist of the Wnt/Wingless pathway

机译：Chibby，Wnt / Wingless途径的核β-连环蛋白相关拮抗剂

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Inappropriate activation of downstream target genes by the oncoprotein β-catenin is implicated in development of numerous human cancers. β-catenin and its fruitfly counterpart Armadillo act as a coactivator in the canonical Wnt/Wingless pathway by binding to Tcf/Lef transcription factors. Here we report a conserved nuclear protein, named Chibby, which was identified in a screen for proteins that directly interact with the C-terminal region of β -catenin. In mammalian cultured cells we demonstrate that Chibby inhibits β-catenin-mediated transcriptional activation by competing with Lef-1 to bind to β-catenin. Inhibition of Drosophila Chibby by RNA interference results in segment polarity defects that mimick a wingless gain-of-function pheno-type, and overexpression of the wingless target genes engrailed and Ultrabithorax. In addition, epistasis experiments indicate that chibby acts downstream of wingless and upstream of armadillo.

机译：癌蛋白β-catenin对下游靶基因的不适当激活与许多人类癌症的发展有关。 β-catenin及其果蝇对应的犰狳通过与Tcf / Lef转录因子结合，在经典Wnt / Wingless途径中充当共激活因子。在这里，我们报告了一个名为Chibby的保守核蛋白，该蛋白在筛选与β-连环蛋白C末端区域直接相互作用的蛋白质的过程中被鉴定出来。在哺乳动物培养的细胞中，我们证明了Chibby通过与Lef-1竞争结合β-catenin抑制β-catenin介导的转录激活。 RNA干扰对果蝇小臂的抑制作用会导致片段极性缺陷，从而模仿无翼功能获得的表型，并导致无翼靶基因过度表达，并导致超胸廓。此外，上位性实验表明，小鸡只在无翅的下游和犰狳的上游起作用。

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《Nature》 |2003年第6934期|p.905-909|共5页
作者
Ken-Ichi Takemaru; Shinji Yamaguchi; Young Sik Lee; Yang Zhang; Richard W. Carthew; Randall T. Moon;
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作者单位

Howard Hughes Medical Institute, Room K536C Health Sciences Building, Campus Box 357750, Department of Pharmacology, and Center for Developmental Biology, University of Washington School of Medicine, Seattle, Washington 98195, USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
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1. An unconventional nuclear localization motif is crucial for function of the Drosophila wnt/wingless antagonist naked cuticle. [J] . Waldrop S, Chan CC, Cagatay T, Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation . 2006,第1期

机译：非常规核定位基序对于果蝇/无翅拮抗剂裸角质层的功能至关重要。
2. An Unconventional Nuclear Localization Motif Is Crucial for Function of the Drosophila Wnt/Wingless Antagonist Naked Cuticle [J] . Chih-Chiang Chan, Judy Mack, Keith A. Wharton, Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation . 2006,第1期

机译：非常规核定位母题对果蝇Wnt /无翅拮抗剂裸角质层的功能至关重要
3. Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway [J] . Sulayman Mokhtarzada Corey Yu Anne Brickenden and Wing-Yiu Choy Biochemistry . 2011,第5期

机译：部分紊乱的人类小鸡的结构表征：对其在Wnt信号通路中的功能的见解。
4. Involvement of Wnt pathway in thyroid cancer around Semipalatinsk Nuclear Test Site [C] . Serik K. Meirmanov, Masahiro Nakashima International Consortium for Medical Care of Hibakusha and Radiation Life Science . 2003

机译：WNT途径在塞古德癌核试验部位周围的甲状腺癌
5. The synthesis and exploration of potential new antagonists of the Wnt signaling pathway: New leads to treat colon cancer? Or, not quite? . [D] . Turbiak, Anjanette J. 2009

机译：Wnt信号通路的潜在新拮抗剂的合成和探索：治疗结肠癌的新方法？还是不完全？。
6. A Wnt/beta-Catenin Pathway Antagonist Chibby Binds Cenexin at the Distal End of Mother Centrioles and Functions in Primary Cilia Formation [O] . Nathan Steere, Vanessa Chae, Michael Burke, 2009

机译：Wnt /β-Catenin通路拮抗剂奇比在母亲中心的远端结合Cenexin，并在初级纤毛形成中起作用。
7. A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation. [O] . Nathan Steere, Vanessa Chae, Michael Burke, 2012

机译：Wnt /β-连环蛋白途径拮抗剂Chibby在母中心体的远端结合Cenexin并在初级纤毛形成中起作用。

Chibby, a nuclear β-catenin-associated antagonist of the Wnt/Wingless pathway

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