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

doi:10.1016/s1534-5807(03)00364-2

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.

Authors

Naoko Kunitoku¹, Takashi Sasayama, Tomotoshi Marumoto, Dongwei Zhang, Shinobu Honda, Osamu Kobayashi, Katsuyoshi Hatakeyama, Yukitaka Ushio, Hideyuki Saya, Toru Hirota

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Aurora Kinase B
Aurora Kinases
Autoantigens*
Cell Nucleus / metabolism
Centromere Protein A
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism*
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins
Kidney / cytology
Kinetochores / enzymology*
Metaphase / physiology
Microtubules / physiology
Mitosis / physiology
Molecular Sequence Data
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Phosphorylation
Prophase / physiology
Protein Serine-Threonine Kinases / metabolism*
Proteins
RNA, Small Interfering
Serine / metabolism

Substances

Autoantigens
CENPA protein, human
Centromere Protein A
Chromosomal Proteins, Non-Histone
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Proteins
RNA, Small Interfering
aryl hydrocarbon receptor-interacting protein
Serine
AURKB protein, human
Aurora Kinase B
Aurora Kinases
Protein Serine-Threonine Kinases