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

104 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cell Nucleus Active Transport
Proto-Oncogenes
Embryonic Structures
Nuclear Proteins
Cells
Messenger RNA
Proteins
Stem cells
Myeloid Leukemia
G2 Phase
Nuclear Envelope
Cell Cycle Checkpoints
Vertebrates
Cell Cycle
Mothers

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214. / Van Deursen, Jan; Boer, Judith; Kasper, Lawryn; Grosveld, Gerard.

In: EMBO Journal, Vol. 15, No. 20, 15.10.1996, p. 5574-5583.

Research output: Contribution to journalArticle

Van Deursen, Jan ; Boer, Judith ; Kasper, Lawryn ; Grosveld, Gerard. / G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214. In: EMBO Journal. 1996 ; Vol. 15, No. 20. pp. 5574-5583.
@article{bedfdf14945b4ccf93eeaf1183db8cb8,
title = "G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214",
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.",
keywords = "CAN(Nup214), Cell cycle, Gene targeting, Nucleocytoplasmic trafficking, Oncogenesis",
author = "{Van Deursen}, Jan and Judith Boer and Lawryn Kasper and Gerard Grosveld",
year = "1996",
month = "10",
day = "15",
language = "English (US)",
volume = "15",
pages = "5574--5583",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "20",

}

TY - JOUR

T1 - G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214

AU - Van Deursen, Jan

AU - Boer, Judith

AU - Kasper, Lawryn

AU - Grosveld, Gerard

PY - 1996/10/15

Y1 - 1996/10/15

N2 - 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.

AB - 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.

KW - CAN(Nup214)

KW - Cell cycle

KW - Gene targeting

KW - Nucleocytoplasmic trafficking

KW - Oncogenesis

UR - http://www.scopus.com/inward/record.url?scp=0029903414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029903414&partnerID=8YFLogxK

M3 - Article

C2 - 8896451

AN - SCOPUS:0029903414

VL - 15

SP - 5574

EP - 5583

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 20

ER -