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 Ca²⁺-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 Ca²⁺-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 Ca²⁺. Structured summary: MINT- 8045244: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with S100A2 (uniprotkb: P29034) by pull down (MI: 0096). MINT- 8044928: Importin alpha (uniprotkb: P52292) binds (MI: 0407) to S100A6 (uniprotkb: P06703) by pull down (MI: 0096). MINT- 8044941: Importin alpha (uniprotkb: P52292) and S100A6 (uniprotkb: P06703) bind (MI: 0407) by electrophoretic mobility supershift assay (MI: 0412). MINT- 8044997: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with S100A6 (uniprotkb: P06703) by anti bait coimmunoprecipitation (MI: 0006). MINT- 8045031: Importin beta (uniprotkb: Q14974) physically interacts (MI: 0915) with importin alpha (uniprotkb: P52293) and S100A6 (uniprotkb: P06703) by pull down (MI: 0096). MINT- 8044917: Importin alpha (uniprotkb: P52292) binds (MI: 0407) to S100A2 (uniprotkb: P29034) by pull down (MI: 0096). MINT- 8045257: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with S100A6 (uniprotkb: P06703) by pull down (MI: 0096). MINT- 8045015: Importin beta (uniprotkb: Q14974) physically interacts (MI: 0915) with importin alpha (uniprotkb: P52293) and S100A2 (uniprotkb: P29034) by pull down (MI: 0096). MINT- 8045267: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with S100A2 (uniprotkb: P29034) and npm2 (uniprotkb: Q6GQG6) by pull down (MI: 0096). MINT- 8045316: Importin beta (uniprotkb: Q14974) physically interacts (MI: 0915) with importin alpha (uniprotkb: P52293) by pull down (MI: 0096). MINT- 8045302: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with NPM1 (uniprotkb: P06748) and S100A2 (uniprotkb: P29034) by pull down (MI: 0096). MINT- 8045290: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with npm2 (uniprotkb: Q6GQG6) by pull down (MI: 0096). MINT- 8044963, MINT- 8044985: Importin alpha (uniprotkb: P52292) physically interacts (MI: 0915) with S100A2 (uniprotkb: P29034) by anti bait coimmunoprecipitation (MI: 0006). MINT- 8044951: Importin alpha (uniprotkb: P52292) and S100A2 (uniprotkb: P29034) bind (MI: 0407) by electrophoretic mobility supershift assay (MI: 0412).