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Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Molecular Biology Organization
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365428/ https://www.ncbi.nlm.nih.gov/pubmed/22510880 http://dx.doi.org/10.1038/emboj.2012.91 |
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author | 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 |
author_facet | 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 |
author_sort | Wilson, Catherine H |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3365428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | European Molecular Biology Organization |
record_format | MEDLINE/PubMed |
spelling | pubmed-33654282012-06-01 Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation 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 EMBO J Article 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. European Molecular Biology Organization 2012-05-30 2012-04-17 /pmc/articles/PMC3365428/ /pubmed/22510880 http://dx.doi.org/10.1038/emboj.2012.91 Text en Copyright © 2012, European Molecular Biology Organization https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. |
spellingShingle | Article 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 Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
title | Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
title_full | Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
title_fullStr | Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
title_full_unstemmed | Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
title_short | Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
title_sort | nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365428/ https://www.ncbi.nlm.nih.gov/pubmed/22510880 http://dx.doi.org/10.1038/emboj.2012.91 |
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