G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214

Jan Van Deursen, Judith Boer, Lawryn Kasper, Gerard Grosveld

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

The vertebrate nucleopore complex (NPC) is a 125 MDa multiprotein assembly that mediates nucleocytoplasmic transport. One of its components, CAN/Nup214, is an FXFG repeat-containing protein known to be involved in myeloid leukemia in humans. We have devised a powerful genetic approach, using maternally derived protein in murine null embryos, to show that CAN/ Nup214 is essential for NPC function in vivo. We demonstrate that CAN-/- mouse embryonic stem (ES) cells are not viable and that CAN-/- embryos die in utero between 4.0 and 4.5 days postcoitum, following the depletion of their CAN from maternal sources. In 3.5-day-old mutant embryos, cultured in vitro, progressive depletion of CAN leads to cell cycle arrest in G2 phase, and eventually to blastocoel collapse, impaired NLS-mediated protein uptake and nuclear accumulation of polyadenylated RNA. Remarkably, these defective CAN-depleted embryos do not display any gross morphological abnormalities in their nuclear envelopes or NPCs. Our data suggest that CAN is critical to cell cycle progression and required for both nuclear protein import and mRNA export.

Original languageEnglish (US)
Pages (from-to)5574-5583
Number of pages10
JournalEMBO Journal
Volume15
Issue number20
StatePublished - Oct 15 1996

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Keywords

  • CAN(Nup214)
  • Cell cycle
  • Gene targeting
  • Nucleocytoplasmic trafficking
  • Oncogenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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