NF-κB p52, RelB and c-Rel are transported into the nucleus via a subset of importin α molecules

In resting cells NF-kappa B transcription factors are retained in the cytoplasm as latent inactive complexes, until they are activated and rapidly transported into the nucleus. We show that all NF-kappa B proteins are imported into the nucleus via a subset of importin a isoforms. Our data indicate that the NF-kappa B components of the classical and alternative pathways have somewhat different specifities to importin a molecules. Based on the results from binding experiments of in vitro-translated and Sendai virus infection-induced or TNF-alpha-stimulated endogenous NF-kappa B proteins, it can be predicted that the specifity of NF-kappa B proteins to importin alpha molecules is different and changes upon the composition of the imported dimer. p52 protein binds directly to importin alpha 3, alpha 4, alpha 5 and alpha 6 and c-Rel binds to importin alpha 5, alpha 6 and alpha 7 via a previously described monopartite nuclear localization signals (NLSs). Here we show that RelB, instead, has a bipartite arginine/lysine-rich NLS that mediates the binding of RelB to importin alpha 5 and alpha 6 and subsequent nuclear translocation of the protein. Moreover, we show that the nuclear import of p52/RelB heterodimers is mediated exclusively by the NLS of RelB. In addition, we found that the NLS of p52 mediates the nuclear import of p52/p65 heterodimers. (c) 2008 Elsevier Inc. All rights reserved.