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http://dx.doi.org/10.5483/BMBRep.2014.47.11.250

Aurora-A kinase-inactive mutants disrupt the interaction with Ajuba and cause defects in mitotic spindle formation and G2/M phase arrest in HeLa cells  

Bai, Meirong (state Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Ni, Jun (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Shen, Suqin (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Huang, Qiang (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Wu, Jiaxue (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Le, Yichen (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Yu, Long (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Publication Information
BMB Reports / v.47, no.11, 2014 , pp. 631-636 More about this Journal
Abstract
Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. We previously reported an intramolecular inhibitory regulation of Aurora-A between its N-terminal regulatory domain (Nt, amino acids [aa] 1-128) and the C-terminal catalytic domain (Cd, aa 129-403). Here, we demonstrate that although both Aurora-A mutants (AurA-K250G and AurA-D294G/Y295G) lacked interactions between the Nt and Cd, they also failed to interact with Ajuba, an essential activator of Aurora-A, leading to loss of kinase activity. Additionally, overexpression of either of the mutants resulted in centrosome amplification and mitotic spindle formation defects. Both mutants were also able to cause G2/M arrest and apoptosis. These results indicate that both K250 and D294/Y295 are critical for direct interaction between Aurora-A and Ajuba and the function of the Aurora-A complex in cell cycle progression.
Keywords
Ajuba; Aurora-A; Autophosphorylation; Cell cycle; Centrosome;
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