Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-kappa B

Nozomi Takahashi*, Jeroen W. J. van Kilsdonk, Benedikt Ostendorf, Ruben Smeets, Sophia W. M. Bruggeman, Angel Alonso, Fons van de Loo, Matthias Schneider, Wim B. van den Berg, Guido W. M. Swart

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Scopus)

Abstract

Nucleoporin 88 kDa (Nup88) is a tumor marker, overexpressed in various types of cancer. In Drosophila Nup88 (mbo) was reported to selectively mediate the nucleocytoplasmic transport of NF-kappa B, an Ubiquitous transcription factor involved in immune responses, apoptosis, and cancer. We addressed the function of Nup88 in mammalian cells. Selective depletion of Nup88 by small interfering RNA (siRNA) inhibited NF-kappa B-dependent reporter gene activation and the nuclear translocation of NF-kappa B without affecting the Upstream activation pathway in NIH3T3 cells. In contrast, nuclear translocation of glucocorticoid receptor was not reduced by the depletion of Nup88. In metastatic melanoma cells overexpressing NUP88, constitutive activation of NF-kappa B was found both in nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear accumulation of NF-kappa B subunits. We conclude that Nup88 regulates the activity of NF-kappa B at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-kappa B activation. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)424-430
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume374
Issue number3
DOIs
Publication statusPublished - 26-Sept-2008

Keywords

  • nuclear pore complex
  • NF-kappa B
  • nucleocytoplasmic transport
  • nucleoporin
  • cancer cells
  • reporter gene assay
  • NUCLEAR-PORE COMPLEX
  • PROTEIN EXPORT
  • NUP88
  • IMPORT
  • CANCER
  • ACTIVATION
  • DROSOPHILA
  • CELLS
  • CRM1
  • AGGRESSIVENESS

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