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

Naoko Kunitoku, Takashi Sasayama, Tomotoshi Marumoto, Dongwei Zhang, Shinobu Honda, Osamu Kobayashi, Katsuyoshi Hatakeyama, Yukitaka Ushio, Hideyuki Saya, Toru Hirota

Research output: Contribution to journalArticle

183 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)853-864
Number of pages12
JournalDevelopmental Cell
Volume5
Issue number6
DOIs
Publication statusPublished - 2003 Dec
Externally publishedYes

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Kinetochores
Prophase
Phosphorylation
Centromere
Mitosis
Prometaphase
Chromosomes
RNA Interference
Microtubules
centromere protein A
Phosphotransferases
Cells
RNA
Defects
Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function. / Kunitoku, Naoko; Sasayama, Takashi; Marumoto, Tomotoshi; Zhang, Dongwei; Honda, Shinobu; Kobayashi, Osamu; Hatakeyama, Katsuyoshi; Ushio, Yukitaka; Saya, Hideyuki; Hirota, Toru.

In: Developmental Cell, Vol. 5, No. 6, 12.2003, p. 853-864.

Research output: Contribution to journalArticle

Kunitoku, N, Sasayama, T, Marumoto, T, Zhang, D, Honda, S, Kobayashi, O, Hatakeyama, K, Ushio, Y, Saya, H & Hirota, T 2003, 'CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function', Developmental Cell, vol. 5, no. 6, pp. 853-864. https://doi.org/10.1016/S1534-5807(03)00364-2
Kunitoku, Naoko ; Sasayama, Takashi ; Marumoto, Tomotoshi ; Zhang, Dongwei ; Honda, Shinobu ; Kobayashi, Osamu ; Hatakeyama, Katsuyoshi ; Ushio, Yukitaka ; Saya, Hideyuki ; Hirota, Toru. / CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function. In: Developmental Cell. 2003 ; Vol. 5, No. 6. pp. 853-864.
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