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.
Fu
Jingyan
J
The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing 100871, China.
Bian
Minglei
M
Liu
Junjun
J
Jiang
Qing
Q
Zhang
Chuanmao
C
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D022004:Chromosome Structures / Q000378:metabolism; D017124:Conserved Sequence; D004789:Enzyme Activation; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013379:Substrate Specificity
D000596:Amino Acids; D002868:Chromosomal Proteins, Non-Histone; D008869:Microtubule-Associated Proteins; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D005998:Glycine