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果蝇Wg信号通路的抑制涉及Mad与犰狳蛋白/β-连环蛋白之间对dTcf结合的竞争。

Inhibition of Drosophila Wg signaling involves competition between Mad and Armadillo/beta-catenin for dTcf binding.

作者信息

Zeng Yi Arial, Rahnama Maryam, Wang Simon, Lee Wendy, Verheyen Esther M

机构信息

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.

出版信息

PLoS One. 2008;3(12):e3893. doi: 10.1371/journal.pone.0003893. Epub 2008 Dec 9.

DOI:10.1371/journal.pone.0003893
PMID:19065265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2587708/
Abstract

Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor beta (TGFbeta)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector beta-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf.

摘要

精确调控的信号转导通路对于发育事件的调控和肿瘤发生的预防至关重要。转化生长因子β（TGFβ）/骨形态发生蛋白（BMP）和Wnt/无翅（Wg）通路在生物体的模式形成和生长中都起着重要作用，它们的失调会导致癌症。我们描述了果蝇Wg和BMP信号之间的一种相互作用机制，其中Wg靶基因的表达受到BMP信号的拮抗。在体内，活化的BMP受体和BMP效应分子Mad的高水平都能抑制Wg靶基因的表达。相反，mad的缺失会诱导Wg靶基因的表达。此外，我们发现Wg转录因子dTcf在体内的异位表达能够抑制异位Mad引起的抑制作用。体外结合研究揭示了Mad和Wnt效应分子β-连环蛋白/犰狳（Arm）之间对dTcf结合的竞争。我们的体内遗传分析和靶基因研究支持了一种与体外结合和竞争研究一致的机制，即BMP通路成分可以通过影响Arm和dTcf的结合来抑制Wg靶基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/cd7f991eebdd/pone.0003893.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/d6dc9eb868e1/pone.0003893.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/a12886a693f0/pone.0003893.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/c1951aeeca8f/pone.0003893.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/cacb2a5d622c/pone.0003893.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/595718f6f4c0/pone.0003893.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/cd7f991eebdd/pone.0003893.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/d6dc9eb868e1/pone.0003893.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/a12886a693f0/pone.0003893.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/c1951aeeca8f/pone.0003893.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/cacb2a5d622c/pone.0003893.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/595718f6f4c0/pone.0003893.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc40/2587708/cd7f991eebdd/pone.0003893.g006.jpg

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