CLONING AND CHARACTERIZATION OF HUMAN KARYOPHERIN BETA-3

Nuclear import of classical nuclear localization sequence-bearing prot eins is mediated by karyopherin alpha/beta 1 heterodimers, A second nu clear import pathway, mediated by karyopherin beta 2 (transportin), re cently was described for mRNA-binding proteins. Here we report the clo ning and characterization of human karyopherin beta 3, which may be in volved in a third pathway for nuclear import. Karyopherin beta 3 was l ocalized mainly to the cytosol and the nucleus, particularly the nucle ar rim. It bound to several of the repeat-containing nucleoporins (Nup 358, Nup214, Nup153, Nup98, and p62) in overlay and solution-binding a ssays and was competed away by karyopherin beta 1. For Nup98, we local ized this binding to the peptide repeat-containing region, Karyopherin beta 3 contains two putative Ran-binding homology regions and bound t o Ran-GTP in a solution-binding assay with much higher affinity than t o Ran-GDP, Furthermore, it interacted with two ribosomal proteins in a n overlay assay, We suggest that karyopherin beta 3 is a nuclear trans port factor that may mediate the import of some ribosomal proteins int o the nucleus.