A transcriptional response to Wnt protein in human embryonic carcinoma cells.
A transcriptional response to Wnt protein in human embryonic carcinoma cells.
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DOI：
10.1186/1471-213x-2-8
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发表时间：
2002-07-02
影响因子：
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通讯作者：
Nusse, Roel
中科院分区：
文献类型：
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作者：
Willert, Jennifer;Epping, Mirjam;Pollack, Jonathan R;Brown, Patrick O;Nusse, Roel
Wnt信号转导与许多发育决定有关，包括干细胞控制以及癌症。已知Wnt途径的靶基因相对较少。我们已经确定了Wnt信号转导的靶基因，利用芯片技术和人胚胎癌细胞激活Wnt蛋白。加入Wnt后早期上调的约50个基因包括先前已知的Wnt靶点Cyclin D1、MYC、ID 2和βTRCP。新发现的靶点包括MSX 1、MSX 2、Nucleophosmin、Follistatin、TLE/Groucho、Ubc 4/5E 2、CBP/P300、Frizzled和REST/NRSF，它们对理解Wnt在发育和癌症中的作用具有重要意义。蛋白质合成抑制剂放线菌酮阻断Wnt的诱导作用，这与靶基因激活前需要新合成的β-连环蛋白一致。我们发现的几乎所有靶基因的启动子都具有假定的TCF结合位点，并且我们表明TCF结合位点是诱导卵泡抑素所必需的。几个靶基因对Wnt和BMP的组合具有协同反应。Wnt信号激活促进干细胞命运和抑制细胞分化的基因，并调节参与其自身信号系统的大量基因。
Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway. We have identified target genes of Wnt signaling using microarray technology and human embryonic carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and βTRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized β-catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites, and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP. Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation and regulates a remarkable number of genes involved in its own signaling system.