The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88

Maarten Fornerod, Jan Van Deursen, Sjozef Van Baal, Albert Reynolds, Donna Davis, K. Gopal Murti, Jack Fransen, Gerard Grosveld

Research output: Contribution to journalArticle

383 Scopus citations

Abstract

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-β, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

Original languageEnglish (US)
Pages (from-to)807-816
Number of pages10
JournalEMBO Journal
Volume16
Issue number4
DOIs
StatePublished - Feb 17 1997

Keywords

  • CAN
  • CSE1
  • Importin-β
  • Nuclear pore complex
  • Nucleocytoplasmic transport
  • Nup214

ASJC Scopus subject areas

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

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    Fornerod, M., Van Deursen, J., Van Baal, S., Reynolds, A., Davis, D., Murti, K. G., Fransen, J., & Grosveld, G. (1997). The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. EMBO Journal, 16(4), 807-816. https://doi.org/10.1093/emboj/16.4.807