Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation.
Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation.
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DOI：
10.1038/emboj.2012.91
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发表时间：
2012-05-30
期刊：
影响因子：
11.4
通讯作者：
Adams, David J.
中科院分区：
文献类型：
--
作者：
Wilson, Catherine H.;Crombie, Catriona;van der Weyden, Louise;Poulogiannis, George;Rust, Alistair G.;Pardo, Mercedes;Gracia, Tannia;Yu, Lu;Choudhary, Jyoti;Poulin, Gino B.;McIntyre, Rebecca E.;Winton, Douglas J.;March, H. Nikki;Arends, Mark J.;Fraser, Andrew G.;Adams, David J.
简单模型生物体的遗传筛选已经鉴定出保守信号转导途径的许多关键成分，这些成分在调节不当时会致癌。在这里，我们将H37N21.1确定为在let-60（n1046gf）中调节外阴诱导的基因，let-60（n1046gf是一种在秀丽隐杆线虫Ras直系同源物中具有功能获得性突变的菌株），并表明Nrbp1（该基因的小鼠直系同源物）的体细胞缺失会导致肠道祖细胞表型，从而导致所有肠道细胞的增殖和分化发生深刻变化。血统。我们表明，Nrbp1 与泛素化机制的关键组件相互作用，并且肠道中 Nrbp1 的丢失会导致干细胞命运的关键介质 Sall4 和 Tsc22d2 的积累。我们还发现，Nrbp1 的体细胞缺失会导致肿瘤发生，其中血液肿瘤和肠道肿瘤占主导地位，并且核受体结合蛋白 1 (NRBP1) 在一系列人类肿瘤中表达下调，其中低表达与不良预后相关。因此，NRBP1 是细胞命运的保守调节因子，在肿瘤抑制中发挥着重要作用。
Genetic screens in simple model organisms have identified many of the key components of the conserved signal transduction pathways that are oncogenic when misregulated. Here, we identify H37N21.1 as a gene that regulates vulval induction in let-60(n1046gf), a strain with a gain-of-function mutation in the Caenorhabditis elegans Ras orthologue, and show that somatic deletion of Nrbp1, the mouse orthologue of this gene, results in an intestinal progenitor cell phenotype that leads to profound changes in the proliferation and differentiation of all intestinal cell lineages. We show that Nrbp1 interacts with key components of the ubiquitination machinery and that loss of Nrbp1 in the intestine results in the accumulation of Sall4, a key mediator of stem cell fate, and of Tsc22d2. We also reveal that somatic loss of Nrbp1 results in tumourigenesis, with haematological and intestinal tumours predominating, and that nuclear receptor binding protein 1 (NRBP1) is downregulated in a range of human tumours, where low expression correlates with a poor prognosis. Thus NRBP1 is a conserved regulator of cell fate, that plays an important role in tumour suppression.
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影响因子：
11.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Adams, DJ;Quail, MA;Bradley, A
通讯作者：
Bradley, A