TY - JOUR
T1 - CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function
AU - Kunitoku, Naoko
AU - Sasayama, Takashi
AU - Marumoto, Tomotoshi
AU - Zhang, Dongwei
AU - Honda, Shinobu
AU - Kobayashi, Osamu
AU - Hatakeyama, Katsuyoshi
AU - Ushio, Yukitaka
AU - Saya, Hideyuki
AU - Hirota, Toru
N1 - Funding Information:
We thank Drs. J.-M. Peters and S. Hauf (Research Institute of Molecular Pathology, Vienna), D.O. Morgan (University of California, San Francisco), and T. Iwanaga (Hokkaido University) for valuable discussions; K. Yoda (Nagoya University) for antibodies to CENP-A; T.J. Yen (Fox Chase Cancer Center, Philadelphia) for antibodies to BubR1 and CENP-E; Y. Fukushima in preparation of the manuscript; and members of the Gene Technology Center at Kumamoto University for technical support. T.H. is a postdoctoral fellow of the Japan Society for the Promotion of Science (JSPS). This work was supported by the Ministry of Education, Science, Sports, and Culture of Japan and the Research for the Future program of JSPS (H.S.).
PY - 2003/12
Y1 - 2003/12
N2 - The Aurora (Ipl1)-related kinases are universal regulators of mitosis. We now show that Aurora-A, in addition to Aurora-B, regulates kinetochore function in human cells. A two-hybrid screen identified the kinetochore component CENP-A as a protein that interacts with Aurora-A. Aurora-A phosphorylated CENP-A in vitro on Ser-7, a residue also known to be targeted by Aurora-B. Depletion of Aurora-A or Aurora-B by RNA interference revealed that CENP-A is initially phosphorylated in prophase in a manner dependent on Aurora-A, and that this reaction appears to be required for the subsequent Aurora-B-dependent phosphorylation of CENP-A as well as for the restriction of Aurora-B to the inner centromere in prometaphase. Prevention of CENP-A phosphorylation also led to chromosome misalignment during mitosis as a result of a defect in kinetochore attachment to microtubules. Our observations suggest that phosphorylation of CENP-A on Ser-7 by Aurora-A in prophase is essential for kinetochore function.
AB - The Aurora (Ipl1)-related kinases are universal regulators of mitosis. We now show that Aurora-A, in addition to Aurora-B, regulates kinetochore function in human cells. A two-hybrid screen identified the kinetochore component CENP-A as a protein that interacts with Aurora-A. Aurora-A phosphorylated CENP-A in vitro on Ser-7, a residue also known to be targeted by Aurora-B. Depletion of Aurora-A or Aurora-B by RNA interference revealed that CENP-A is initially phosphorylated in prophase in a manner dependent on Aurora-A, and that this reaction appears to be required for the subsequent Aurora-B-dependent phosphorylation of CENP-A as well as for the restriction of Aurora-B to the inner centromere in prometaphase. Prevention of CENP-A phosphorylation also led to chromosome misalignment during mitosis as a result of a defect in kinetochore attachment to microtubules. Our observations suggest that phosphorylation of CENP-A on Ser-7 by Aurora-A in prophase is essential for kinetochore function.
UR - https://www.scopus.com/pages/publications/10744225982
UR - https://www.scopus.com/pages/publications/10744225982#tab=citedBy
U2 - 10.1016/S1534-5807(03)00364-2
DO - 10.1016/S1534-5807(03)00364-2
M3 - Article
C2 - 14667408
AN - SCOPUS:10744225982
SN - 1534-5807
VL - 5
SP - 853
EP - 864
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -