title: Nuclear import of human histone lysine-specific demethylase LSD1.
abstract: Upregulation and nuclear retention of the human histone demethylase LSD1 are correlated with aggressiveness and poor outcome of several cancer types, but the molecular mechanism of LSD1 nuclear import remains unclear. Here, we found that the N-terminal flexible region of LSD1 contains a nuclear localization signal (NLS), (112)RRKRAK(117). Mutation or deletion of the NLS completely abolished the nuclear import of LSD1, suggesting the motif is a bona fide NLS. More importantly, our GST pull-down assay showed that LSD1 physically interacts with three proteins of importin α family. In addition, our data suggest that the nuclear localization of LSD1 via the NLS is not a cell-type specific event. Thus, these findings demonstrate for the first time that the NLS motif within the N-terminal flexible domain of LSD1 is critical for its nuclear localization via interaction with importin α proteins.
authors.affiliation: Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea. Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea. Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Min Seong
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea. Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Min Aeh
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea. Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Su Hyung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea. Department of Medical Genetics, College of Medicine, Yanbian University, 977 Gongyuan Road, Yanji City, China; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; and Initiative for Biological Function and Systems, Yonsei University, Seoul 120-749, Republic of Korea. ykjang@yonsei.ac.kr.
authors.forename: Yeun Kyu
authors.initials: YK
authors.lastname: Jang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D057809:HEK293 Cells; D056466:Histone Demethylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D019913:Nuclear Localization Signals / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D028901:alpha Karyopherins / Q000378:metabolism
chemical_list: D019913:Nuclear Localization Signals; D028901:alpha Karyopherins; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Importinα; N-terminal flexible region; histone demethylase LSD1; nuclear localization signal; β