TY - JOUR
T1 - Poly-ADP Ribosylation of Miki by tankyrase-1 Promotes Centrosome Maturation
AU - Ozaki, Yuko
AU - Matsui, Hirotaka
AU - Asou, Hiroya
AU - Nagamachi, Akiko
AU - Aki, Daisuke
AU - Honda, Hiroaki
AU - Yasunaga, Shin'ichiro
AU - Takihara, Yoshihiro
AU - Yamamoto, Tadashi
AU - Izumi, Shunsuke
AU - Ohsugi, Miho
AU - Inaba, Toshiya
N1 - Funding Information:
We thank Drs. N. Oshimori and N. Tokai-Nishizumi for establishment of cell lines and helpful discussion and Ms. M. Nakamura and Mr. N. Yamazaki for excellent technical assistance. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
PY - 2012/9/14
Y1 - 2012/9/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2012.06.033
DO - 10.1016/j.molcel.2012.06.033
M3 - Article
C2 - 22864114
AN - SCOPUS:84866282539
SN - 1097-2765
VL - 47
SP - 694
EP - 706
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -
