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

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

T Sekimoto et al. EMBO J. 1997.

Abstract

In response to interferon-gamma (IFN-gamma), 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 beta subunit (a 97 kDa component) of the nuclear pore-targeting complex via the NPI-1 family, but not the Rch1 family, of alpha subunit (a 58 kDa component) as a result of IFN-gamma stimulation. Antibodies against NPI-1 or beta subunit consistently inhibited the IFN-gamma-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 beta subunit, and that these factors participate in, not only constitutive, but also the conditional nuclear import of proteins.

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