Published in

EMBO Press, The EMBO Journal, 11(31), p. 2486-2497, 2012

DOI: 10.1038/emboj.2012.91

Links

Tools

Export citation

Search in Google Scholar

Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation: Nrbp1 regulates cell fate and tumourigenesis

Journal article published in 2012 by Catherine H. Wilson, Catriona Crombie, Louise van der Weyden, George Poulogiannis, Alistair G. Rust, Mercedes Pardo ORCID, Tannia Gracia, Lu Yu, Jyoti Choudhary ORCID, Gino B. Poulin, Rebecca E. McIntyre, Douglas J. Winton, H. Nikki March, Mark J. Arends, Andrew G. Fraser and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

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.