Characterization of IkappaBalpha nuclear import pathway.
IkappaBalpha controls the transcriptional activity of nuclear factor (NF)-kappaB by retaining it in the cytoplasm; but, when expressed in the nucleus, it can also inhibit the interaction of NF-kappaB with DNA and promote the export of NF-kappaB from the nucleus to the cytoplasm. Here, we report that IkappaBalpha, when not bound to NF-kappaB, is constitutively transported to the nucleus, and we confirm that the interaction of IkappaBalpha with NF-kappaB retains IkappaBalpha in the cytoplasm. Nuclear import of IkappaBalpha does not result from passive diffusion but from a specific energy-dependent transport process that requires the ankyrin repeats of IkappaBalpha. Nuclear accumulation of IkappaBalpha is dependent on importins alpha and beta as well as the small GTPase Ran, which are also responsible for the nuclear import mediated by basic nuclear localization sequences (NLS). However, these proteins are not sufficient to promote IkappaBalpha nuclear translocation. Factor(s) can be removed selectively from cell extracts with ankyrin repeats of IkappaBalpha which strongly reduce import of IkappaBalpha but not of proteins containing basic NLS. These findings indicate that IkappaBalpha is imported in the nucleus by a piggy-back mechanism that involves additional protein(s) containing a basic NLS and able to interact with ankyrin repeats of IkappaBalpha.
Laboratoire de Transport nucléocytoplasmique, Unité Mixte de Recherche 144 Institut Curie-CNRS, 26, rue d'Ulm, 75248 Paris Cedex 05, France.
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D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D016328:NF-kappa B / Q000378:metabolism
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B