TY - JOUR
T1 - BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells
AU - Izumi, H.
AU - Matsumoto, Y.
AU - Ikeuchi, T.
AU - Saya, H.
AU - Kajii, T.
AU - Matsuura, S.
N1 - Funding Information:
We are grateful to Dr S Tanaka for providing anti-pericentrin antibody and Dr M Ohsugi for providing Flag-Plk1 plasmids. We are also grateful to Dr Y Yamamoto and Dr N Watanabe for technical advice. We thank H Ikeda and H Hatakeyama for technical assistance, and T Jo and A Kamesako for secretarial assistance. We also thank our laboratory members for their continuous encouragement. This work was partly carried out at the Analysis Center of Life Science, Hiroshima University. This work was supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture (to HI and to SM), MEXT priority research projects (to HI and to SM) and the Haraguchi Memorial Cancer Grant Foundation (to HI).
PY - 2009/8/6
Y1 - 2009/8/6
N2 - BubR1 is a critical component of the mitotic checkpoint that delays the onset of anaphase until all chromosomes have established bipolar attachment to the microtubules. We previously reported that mutations of the BUB1B gene (encoding BubR1) caused premature chromatid separation (PCS) syndrome, a condition characterized by constitutional aneuploidy and a high risk of childhood cancer. We here report that the cells from PCS syndrome patients have loss of regulation of the centrosome duplication machinery, resulting in centrosome amplification and multipolar mitosis. PCS syndrome cells show increased activity of Polo-like kinase 1 (Plk1), whose knockdown suppresses centrosome amplification. BubR1 localizes to centrosomes, physically interacts with Plk1 and inhibits Plk1 phosphorylation and its kinase activity during interphase. These results unravel a crucial role of BubR1 in preventing centrosome reduplication through negative regulation of Plk1 in interphase cells.
AB - BubR1 is a critical component of the mitotic checkpoint that delays the onset of anaphase until all chromosomes have established bipolar attachment to the microtubules. We previously reported that mutations of the BUB1B gene (encoding BubR1) caused premature chromatid separation (PCS) syndrome, a condition characterized by constitutional aneuploidy and a high risk of childhood cancer. We here report that the cells from PCS syndrome patients have loss of regulation of the centrosome duplication machinery, resulting in centrosome amplification and multipolar mitosis. PCS syndrome cells show increased activity of Polo-like kinase 1 (Plk1), whose knockdown suppresses centrosome amplification. BubR1 localizes to centrosomes, physically interacts with Plk1 and inhibits Plk1 phosphorylation and its kinase activity during interphase. These results unravel a crucial role of BubR1 in preventing centrosome reduplication through negative regulation of Plk1 in interphase cells.
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U2 - 10.1038/onc.2009.141
DO - 10.1038/onc.2009.141
M3 - Article
C2 - 19503101
AN - SCOPUS:68349155746
VL - 28
SP - 2806
EP - 2820
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 31
ER -