Insights into the non-mitotic functions of Aurora kinase A: more than just cell division

被引:55
作者
Bertolin, Giulia [1 ]
Tramier, Marc [1 ]
机构
[1] Univ Rennes, CNRS, IGDR Genet & Dev Inst Rennes, UMR 6290, F-35000 Rennes, France
关键词
AURKA; Cell cycle; Non-mitotic roles; Structural data; Fluorescence microscopy; FRET; TO-MESENCHYMAL TRANSITION; SMALL-MOLECULE INHIBITOR; A KINASE; C-MYC; CENTROSOME AMPLIFICATION; MITOCHONDRIAL FISSION; SPINDLE MICROTUBULES; CANCER CELLS; SELF-RENEWAL; CYCLE ARREST;
D O I
10.1007/s00018-019-03310-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
AURKA is a serine/threonine kinase overexpressed in several cancers. Originally identified as a protein with multifaceted roles during mitosis, improvements in quantitative microscopy uncovered several non-mitotic roles as well. In physiological conditions, AURKA regulates cilia disassembly, neurite extension, cell motility, DNA replication and senescence programs. In cancer-like contexts, AURKA actively promotes DNA repair, it acts as a transcription factor, promotes cell migration and invasion, and it localises at mitochondria to regulate mitochondrial dynamics and ATP production. Here we review the non-mitotic roles of AURKA, and its partners outside of cell division. In addition, we give an insight into how structural data and quantitative fluorescence microscopy allowed to understand AURKA activation and its interaction with new substrates, highlighting future developments in fluorescence microscopy needed to better understand AURKA functions in vivo. Last, we will recapitulate the most significant AURKA inhibitors currently in clinical trials, and we will explore how the non-mitotic roles of the kinase may provide new insights to ameliorate current pharmacological strategies against AURKA overexpression.
引用
收藏
页码:1031 / 1047
页数:17
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