Regulation of nuclear localization signal-importin α interaction by Ca2+/S100A6.
Although the precise intracellular roles of S100 proteins are not fully understood, these proteins are thought to be involved in Ca(2+)-dependent diverse signal transduction pathways. In this report, we identified importin α as a novel target of S100A6. Importin α contains armadillo repeats, essential for binding to nuclear localization signals. Based on the results from GST pull-down assay, gel-shift assay, and co-immunoprecipitation, we demonstrated that S100A6 specifically interacts with the armadillo repeats of importin α in a Ca(2+)-dependent manner, resulting in inhibition of the nuclear localization signal (NLS)-importin α complex formation in vitro and in vivo. These results indicate S100A6 may regulate the nuclear transport of NLS-cargos in response to increasing concentrations of intracellular Ca(2+).
Department of Signal Transduction Sciences, Kagawa University, Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Maki
M
Takata
Seiko
S
Shimamoto
Fuminori
F
Yamaguchi
Masaaki
M
Tokuda
Hiroshi
H
Tokumitsu
Ryoji
R
Kobayashi
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D009418:S100 Proteins / Q000378:metabolism*; D013539:Simian virus 40; D028901:alpha Karyopherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism
D019913:Nuclear Localization Signals; D009418:S100 Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins; D002118:Calcium