Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1

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Abstract
In response to interferon‐γ (IFN‐γ), Stat1 is tyrosine phosphorylated and translocates to the nucleus where it activates transcription. In this study, we identified factors which mediate the nuclear import of Stat1. Tyrosine‐phosphorylated Stat1 associated with the β subunit (a 97 kDa component) of the nuclear pore‐targeting complex via the NPI‐1 family, but not the Rch1 family, of α subunit (a 58 kDa component) as a result of IFN‐γ stimulation. Antibodies against NPI‐1 or β subunit consistently inhibited the IFN‐γ‐dependent nuclear import of Stat1 in living cells, although antibodies reactive to Rch1 had no effect. Solution binding assays with deletion mutants of NPI‐1 showed that the Stat1‐binding domain of NPI‐1 was located in the carboxy‐terminal region, which is clearly distinct from the SV40 large T antigen nuclear localization signal (NLS)‐binding region. These results indicate that the extracellular signal‐dependent nuclear transport of Stat1 is mediated by NPI‐1, but not Rch1, in conjunction with β subunit, and that these factors participate in, not only constitutive, but also the conditional nuclear import of proteins.