title: Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation.
abstract: During prometaphase, dense microtubule nucleation sites at centrosomes form robust spindles that align chromosomes promptly. Failure of centrosome maturation leaves chromosomes scattered, as seen routinely in cancer cells, including myelodysplastic syndrome (MDS). We previously reported that the Miki (LOC253012) gene is frequently deleted in MDS patients, and that low levels of Miki are associated with abnormal mitosis. Here we demonstrate that Miki localizes to the Golgi apparatus and is poly(ADP-ribosyl)ated by tankyrase-1 during late G2 and prophase. PARsylated Miki then translocates to mitotic centrosomes and anchors CG-NAP, a large scaffold protein of the γ-tubulin ring complex. Due to impairment of microtubule aster formation, cells in which tankyrase-1, Miki, or CG-NAP expression is downregulated all show prometaphase disturbances, including scattered and lagging chromosomes. Our data suggest that PARsylation of Miki by tankyrase-1 is a key initial event promoting prometaphase.
authors.affiliation: Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsui
authors.forename: Hiroya
authors.initials: H
authors.lastname: Asou
authors.forename: Akiko
authors.initials: A
authors.lastname: Nagamachi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Honda
authors.forename: Shin'ichiro
authors.initials: S
authors.lastname: Yasunaga
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takihara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Izumi
authors.forename: Miho
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inaba
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000737:chemistry / Q000378:metabolism*; D006056:Golgi Apparatus / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000737:chemistry / Q000378:metabolism; D038501:Tankyrases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D011064:Poly Adenosine Diphosphate Ribose; D011506:Proteins; D038501:Tankyrases; C577318:HEPACAM2 protein, human; C024857:poly(ADP)-ribosylated proteins; C418109:TNKS protein, human