2. Academic Validation
  3. CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function

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

  • Dev Cell. 2003 Dec;5(6):853-64. doi: 10.1016/s1534-5807(03)00364-2.
Naoko Kunitoku 1,  Takashi Sasayama,  Tomotoshi Marumoto,  Dongwei Zhang,  Shinobu Honda,  Osamu Kobayashi,  Katsuyoshi Hatakeyama,  Yukitaka Ushio,  Hideyuki Saya,  Toru Hirota
Affiliations

Affiliation

  • 1 Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
PMID: 14667408 DOI: 10.1016/s1534-5807(03)00364-2
Abstract

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.

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