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

Abstract

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.single amino acid mutation ͉ TPX2 ͉ INCENP ͉ Survivin

Aurora kinases and spindle assembly: Variations on a common theme?

“…Specifically, AurA (G198N) was capable of compensating for the loss of AurB function by forming a complex with INCENP and Survivin and localizing to the inner centromere and the spindle midzone in a manner dependent on its interaction with the components of the CPC. [49][50][51][52] Taken together, these data suggest that the different spatio-temporal distribution and biological functions of AurA and AurB are primarily determined by the nature of their interacting cofactors. If so, can such cofactors, while targeting AurA and AurB to different cellular compartments, still use similar strategies to regulate the kinase activity?…”

A single starfish Aurora kinase performs the combined functions of Aurora-A and Aurora-B in human cells

“…Recently, Fu et al (Fu et al, 2009) and Hans et al (Hans et al, 2009) showed that a single amino acid change within the Aurora-A kinase domain (Gly198 to the equivalent Asn residue of Aurora-B) is sufficient to convert it into an Aurora-B-like kinase in HeLa cells. The equivalent residue in ApAurora (supplementary material Fig.…”

Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for Efficient Cell Cycle Progression

“…Aurora kinases exert multiple roles in diverse cell cycle-related processes by phosphorylating a wide variety of substrates (Biggins and Murray, 2001;Carmena et al, 2009;Fu et al, 2009;Hans et al, 2009;Van Damme et al, 2011;Petrovská et al, 2012;Hochegger et al, 2013;Demidov et al, 2014;Goldenson and Crispino, 2015;Weimer et al, 2015). However, to date, only histone H3 (Hsu et al, 2000) and TPX2 have been reported as alpha Aurora substrates in plants (Demidov et al, 2005;Tomaštíková et al, 2015).…”