2013 Fiscal Year Final Research Report
Roles of impairment of centrosome maturation in leukemogenesis
| Project/Area Number |
23390253
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Hiroshima University |
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Principal Investigator |
INABA Toshiya 広島大学, 原爆放射線医科学研究所, 教授 (60281292)
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| Co-Investigator(Kenkyū-buntansha) |
HONDA Hiroaki 広島大学, 原爆放射線医科学研究所, 教授 (40245064)
MATSUI Hirotaka 広島大学, 原爆放射線医科学研究所, 准教授 (60379849)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 中心体 / 分裂異常 / 骨髄系腫瘍 / モノソミー7 |
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| Research Abstract |
During prometaphase, dense microtubule nucleation sites at centrosomes form robustspindles that align chromosomes promptly. Failure of centrosome maturation leaves chromosomes scattered, as seen 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 g-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 disturbance, 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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Research Products
(10 results)
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[Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function2014
Author(s)
Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
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Journal Title
PLOS ONE
Volume: 9
Pages: e87425
Peer Reviewed
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[Journal Article] Combination therapies with NS5A, NS3 and NS5B inhibitors on different genotypes of hepatitis C virus in human hepatocyte chimeric mice2013
Author(s)
Shi N, Hiraga N, Imamura M, Hayes CN, Zang Y, Kosaka K, Ozaka K, Okazaki A, Murakami E, Tsuge M, Abe H, Aikata H, Takahashi S, Ochi H, Tateno-Mukaidani C, Yoshizato K, Matsui H, Kanai A, Inaba T, McPhee F, Gao M, Chayama K
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Journal Title
Gut
Volume: 62
Pages: 1055-1061
Peer Reviewed
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[Journal Article] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 72013
Author(s)
Nagamachi A, Matsui H, Asou H, Ozaki Y, Aki D, Takubo K, Suda T, Nakamura T, Wolff L, Honda H, Inaba T
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Journal Title
Cancer Cell
Volume: 24
Pages: 305-317
Peer Reviewed
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