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.

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