CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B inner centromeres and for kinetochore function

被引：194

作者：

Kunitoku, N

Sasayama, T

Marumoto, T

Zhang, DW

Honda, S

Kobayashi, O

Hatakeyama, K

Ushio, Y

Saya, H

Hirota, T

机构：

[1] Kumamoto Univ, Dept Tumor Genet & Biol, Grad Sch Med Sci, Kumamoto 8608556, Japan

[2] Kumamoto Univ, Dept Neurosurg, Grad Sch Med Sci, Kumamoto 8608556, Japan

[3] Niigata Univ, Dept Surg, Grad Sch Med & Dent Sci, Niigata 9518510, Japan

来源：

DEVELOPMENTAL CELL | 2003年 / 5卷 / 06期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/S1534-5807(03)00364-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Aurora (IpI1)-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.

引用

页码：853 / 864

页数：12

共 34 条

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