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Publication : Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-kappaB.

First Author  Takahashi N Year  2008
Journal  Biochem Biophys Res Commun Volume  374
Issue  3 Pages  424-30
PubMed ID  18621024 Mgi Jnum  J:138304
Mgi Id  MGI:3804767 Doi  10.1016/j.bbrc.2008.06.128
Citation  Takahashi N, et al. (2008) Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-kappaB. Biochem Biophys Res Commun 374(3):424-30
abstractText  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-kappaB, 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-kappaB-dependent reporter gene activation and the nuclear translocation of NF-kappaB 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-kappaB was found both in nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear accumulation of NF-kappaB subunits. We conclude that Nup88 regulates the activity of NF-kappaB at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-kappaB activation.
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