NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules.
In resting cells NF-kappaB 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-kappaB proteins are imported into the nucleus via a subset of importin alpha isoforms. Our data indicate that the NF-kappaB components of the classical and alternative pathways have somewhat different specifities to importin alpha molecules. Based on the results from binding experiments of in vitro-translated and Sendai virus infection-induced or TNF-alpha-stimulated endogenous NF-kappaB proteins, it can be predicted that the specifity of NF-kappaB proteins to importin alpha molecules is different and changes upon the composition of the imported dimer. p52 protein binds directly to importin alpha3, alpha4, alpha5 and alpha6 and c-Rel binds to importin alpha5, alpha6 and alpha7 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 alpha5 and alpha6 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.
Fagerlund
Riku
R
Department of Viral Diseases and Immunology, National Public Health Institute, FIN-00300, Helsinki, Finland. riku.fagerlund@ktl.fi
Melén
Krister
K
Cao
Xinmin
X
Julkunen
Ilkka
I
D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D007700:Kinetics; D052003:NF-kappa B p52 Subunit / Q000737:chemistry / Q000378:metabolism*; D019913:Nuclear Localization Signals; D020033:Protein Isoforms / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000737:chemistry / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000737:chemistry / Q000378:metabolism*; D028901:alpha Karyopherins / Q000378:metabolism*
C106306:KPNA3 protein, human; D052003:NF-kappa B p52 Subunit; D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D020569:Proto-Oncogene Proteins c-rel; D028901:alpha Karyopherins; D051841:Transcription Factor RelB