Nuclear Receptor Binding Protein 1 Regulates Intestinal Progenitor Cell Homeostasis and Tumour Formation

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Nuclear Receptor Binding Protein 1 Regulates Intestinal Progenitor Cell Homeostasis and Tumour Formation

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Title: Nuclear Receptor Binding Protein 1 Regulates Intestinal Progenitor Cell Homeostasis and Tumour Formation
Author: Wilson, Catherine H; Crombie, Catriona; van der Weyden, Louise; 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; Poulogiannis, George; Adams, David J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Wilson, Catherine H., Catriona Crombie, Louise van der Weyden, George Poulogiannis, Alistair G. Rust, Mercedes Pardo, Tannia Gracia, et al. 2012. Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation. The EMBO Journal 31(11): 2486-2497.
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Abstract: 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.
Published Version: doi:10.1038/emboj.2012.91
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365428/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10417530
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