A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function.

Aurora kinase-A and -B are key regulators of the cell cycle and tumorigenesis. It has remained a mystery why these 2 Aurora kinases, although highly similar in protein sequence and structure, are distinct in subcellular localization and function. Here, we report the striking finding that a single amino acid residue ...
is responsible for these differences. We replaced the Gly-198 of Aurora-A with the equivalent residue Asn-142 of Aurora-B and found that in HeLa cells, Aurora-A(G198N) was recruited to the inner centromere in metaphase and the midzone in anaphase, reminiscent of the Aurora-B localization. Moreover, Aurora-A(G198N) compensated for the loss of Aurora-B in chromosome misalignment and cell premature exit from mitosis. Furthermore, Aurora-A(G198N) formed a complex with the Aurora-B partners, INCENP and Survivin, and its localization depended on this interaction. Aurora-A(G198N) phosphorylated the Aurora-B substrates INCENP and Survivin in vitro. Therefore, we propose that the presence of Gly or Asn at a single site assigns Aurora-A and -B to their respective partners and thus to their distinctive subcellular localizations and functions.
Mesh Terms:
Amino Acid Sequence, Amino Acids, Chromosomal Proteins, Non-Histone, Chromosome Structures, Conserved Sequence, Enzyme Activation, Glycine, HeLa Cells, Humans, Microtubule-Associated Proteins, Mitosis, Models, Molecular, Phosphorylation, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Sequence Alignment, Substrate Specificity
Proc. Natl. Acad. Sci. U.S.A.
Date: Apr. 28, 2009
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