Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-kappaB.
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.
Takahashi
Nozomi
N
Rheumatology Research and Advanced Therapeutics, 272, NCMLS, Radboud University Medical Centre Nijmegen, P.O. Box 9101, Geert Grooteplein 26-28, 6500 HB Nijmegen, The Netherlands. N.Takahashi@reuma.umcn.nl
van Kilsdonk
Jeroen W J
JW
Ostendorf
Benedikt
B
Smeets
Ruben
R
Bruggeman
Sophia W M
SW
Alonso
Angel
A
van de Loo
Fons
F
Schneider
Matthias
M
van den Berg
Wim B
WB
Swart
Guido W M
GW
D021581:Active Transport, Cell Nucleus; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism*
D014408:Biomarkers, Tumor; D028861:Nuclear Pore Complex Proteins; C531116:Nup88 protein, mouse; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D008156:Luciferases