首页> 外文期刊>Nature >A HUMAN MAD PROTEIN ACTING AS A BMP-REGULATED TRANSCRIPTIONAL ACTIVATOR
【24h】

A HUMAN MAD PROTEIN ACTING AS A BMP-REGULATED TRANSCRIPTIONAL ACTIVATOR

机译:人类脂肪蛋白作为BMP调控转录激活因子

获取原文
获取原文并翻译 | 示例
           

摘要

THE TGF-beta/activin/BMP cytokine family signals through serine/threonine kinase receptors, but how the receptors transduce the signal is unknown. The Mad (Mothers against decapentaplegic) gene from Drosophila(1) and the related Sma genes from Caenorhabditis elegans(2) have been genetically implicated in signalling by members of the bone-morphogenetic-protein (BMP) subfamily. We have cloned Smad1, a human homologue of Mad and Sma. Microinjection of Smad1 messenger RNA into Xenopus embryo animal caps mimics the mesoderm-ventralizing effects of BMP4. Smad1 moves into the nucleus in response to BMP4. Smad1 has transcriptional activity when fused to a heterologous DNA-binding domain, and this activity is increased by BMP4 acting through BMP-receptor types I and II. The transactivating activity resides in the conserved carboxy-terminal domain of Smad1 and is disrupted by a nonsense mutation that corresponds to null mutations found in Mad and in the related gene DPC4, a candidate tumour-suppressor gene in human pancreatic cancer(3), Additionally, we show that DPC4 contains a transcriptional activation domain. The results suggests that the Smad proteins are a new class of transcription factors that mediate responses to the TGF-beta family. [References: 23]
机译:TGF-beta /激活素/ BMP细胞因子家族通过丝氨酸/苏氨酸激酶受体发出信号,但是该受体如何转导信号尚不清楚。果蝇(1)的Mad(抗十足功能的母亲)基因和秀丽隐杆线虫(2)的相关Sma基因在遗传上涉及骨形态发生蛋白(BMP)亚家族的信号传导。我们已经克隆了Smad1,这是Mad和Sma的人类同源物。将Smad1信使RNA显微注射到非洲爪蟾胚胎动物帽中,模仿了BMP4的中胚层腹膜化作用。 Smad1响应BMP4进入细胞核。当融合到异源DNA结合域时,Smad1具有转录活性,并且该活性通过BMP4通过I和II型BMP受体的作用而增加。反式激活活性位于Smad1的保守羧基末端结构域中,并被无义突变破坏,该突变对应于Mad和相关基因DPC4中的无效突变,DPC4是人胰腺癌的候选肿瘤抑制基因(3),此外,我们显示DPC4包含一个转录激活域。结果表明,Smad蛋白是一类新的转录因子,可介导对TGF-β家族的反应。 [参考:23]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号