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Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation

Catherine H Wilson1, Catriona Crombie, Louise van der Weyden

  • 1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.

The EMBO Journal
|April 19, 2012
PubMed

Insights

Nuclear receptor binding protein 1 (NRBP1) is a conserved regulator of cell fate. Loss of NRBP1 in mice leads to intestinal abnormalities and tumor formation, suggesting its role in tumor suppression.

Area of Science:

  • Developmental Biology
  • Cancer Biology
  • Genetics

Background:

  • Genetic screens in model organisms identify key components of signal transduction pathways implicated in cancer.
  • Misregulation of these pathways can lead to oncogenesis.

Purpose of the Study:

  • To identify novel genes regulating cell fate and their role in oncogenesis.
  • To investigate the function of H37N21.1 and its mouse orthologue, Nrbp1, in development and cancer.

Main Methods:

  • Genetic screens in Caenorhabditis elegans.
  • Somatic deletion of Nrbp1 in mice.
  • Analysis of intestinal progenitor cell phenotype, proliferation, and differentiation.
  • Investigation of protein interactions with ubiquitination machinery.
  • Analysis of Sall4 and Tsc22d2 accumulation.
  • Tumorigenesis studies in mice.
  • Analysis of NRBP1 expression in human tumors.

Main Results:

  • H37N21.1 regulates vulval induction in C. elegans.
  • Somatic deletion of mouse Nrbp1 causes profound changes in intestinal cell lineages.
  • Loss of Nrbp1 leads to accumulation of Sall4 and Tsc22d2.
  • Somatic Nrbp1 loss results in tumor formation, predominantly hematological and intestinal.
  • NRBP1 is downregulated in human tumors, correlating with poor prognosis.

Conclusions:

  • NRBP1 is a conserved regulator of cell fate.
  • NRBP1 plays a significant role in tumor suppression.
  • Downregulation of NRBP1 is associated with poor prognosis in human cancers.

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