title: PRMT1 promotes mitosis of cancer cells through arginine methylation of INCENP.
abstract: Inner centromere protein (INCENP) is a part of a protein complex known as the chromosomal passenger complex (CPC) that is essential for correcting non-bipolar chromosome attachments and for cytokinesis. We here demonstrate that a protein arginine methyltransferase PRMT1, which are overexpressed in various types of cancer including lung and bladder cancer, methylates arginine 887 in an Aurora Kinase B (AURKB)-binding region of INCENP both in vitro and in vivo. R887-substituted INCENP revealed lower binding-affinity to AURKB than wild-type INCENP in the presence of PRMT1. Knockdown of PRMT1 as well as overexpression of methylation-inactive INCENP attenuated the AURKB activity in cancer cells, and resulted in abnormal chromosomal alignment and segregation. Furthermore, introduction of methylation-inactive INCENP into cancer cells reduced the growth rate, compared with those introduced wild-type INCENP or Mock. Our data unveils a novel mechanism of PRMT1-mediated CPC regulation through methylation of INCENP.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.|Department of Pharmaceutical Analysis, School of Pharmacy, China Medical University, Shenyang, P. R. China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Von Keudell
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakakido
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Piao
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D012097:Repressor Proteins; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: Aurora kinase B; INCENP; PRMT1; arginine methylation