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bioRxiv · 10.1101/274050

Cytoplasmic translocation of nuclear lysine-specific demethylase-1 (LSD1/KDM1A) in human hepatoma cells is induced by its inhibitors

Yabuta, S.·Shidoji, Y.
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Abstract

Histone-modifiable lysine-specific demethylase-1 (LSD1/KDM1A) is often upregulated in many cancers, including hepatoma, and is regarded as oncoprotein. We previously reported that the hepatoma-preventive geranylgeranoic acid (GGA) inhibits KDM1A activity at the same IC50 as that of the clinically used drug tranylcypromine, a verified inhibitor of KDM1A. Here, we report that these inhibitors induced cytoplasmic translocation of nuclear KDM1A in a human hepatoma-derived cell line. Immunofluorescence studies revealed cytoplasmic localization of KDM1A, 3 h after addition of GGA or tranylcypromine in HuH-7 cells. Geranylgeraniol and all-trans retinoic acid were both unable to induce translocation of nuclear KDM1A, whereas farnesoic acid showed the weak activity. Furthermore, GGA did not affect subcellular localization of another histone lysine-specific demethylase, KDM5A. This suggests that the inhibitor-induced translocation of nuclear KDM1A to the cytoplasm is specific for KDM1A. These data demonstrate for the first time that KDM1A inhibitors specifically induce the cytoplasmic translocation of nuclear KDM1A.\n\nAbbreviations

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Yabuta, S., Shidoji, Y.. 2018-03-01. Cytoplasmic translocation of nuclear lysine-specific demethylase-1 (LSD1/KDM1A) in human hepatoma cells is induced by its inhibitors. https://doi.org/10.1101/274050

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