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

Abstract

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 nonmitotic 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 make an insight on 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.

Identification of Pivotal Genes and Pathways in Osteoarthritic Degenerative Meniscal Lesions via Bioinformatics Analysis of the GSE52042 Dataset

“…BIRC5 was detected in human osteoarthritic chondrocytes, and its suppression expression can lead to reduced rates of chondrocyte proliferation and G2/M blockade [55]. Aurora kinase A (AURKA) is a type of Aurora kinase and is crucial for the successful execution of mitosis [56]. AURKA was highly expressed in human osteoarthritic chondrocytes and overexpression of AURKA could contributes to the development of knee osteoarthritis [57].…”

Identification of MicroRNAs With In Vivo Efficacy in Multiple Myeloma-related Xenograft Models

“…miR-137 overexpression together with bortezomib treatment significantly inhibited TG in a MM xenograft model (88). AURKA is required for the correct duplication and separation of the chromosomes during mitosis, but also exhibits non-mitosis-related functions (89). AURKA inhibitors are presently evaluated in clinical studies in patients with MM (90).…”

FOP Negatively Regulates Ciliogenesis and Promotes Cell Cycle Re-entry by Facilitating Primary Cilia Disassembly

“…Several cell cycle-related kinases, such as AURKA and PLK1, have been demonstrated to play essential roles in primary cilia disassembly (Pugacheva et al, 2007;Inoko et al, 2012;Lee et al, 2012;Plotnikova et al, 2012Plotnikova et al, , 2015Wang et al, 2013;Miyamoto et al, 2015). AURKA is mainly involved in mitotic events, such as centrosome duplication, separation and maturation, and spindle formation (Bertolin and Tramier, 2020). In the process of cilia disassembly, it can be phosphorylated and activated by HEF1 and other proteins.…”

“…AURKA is mainly involved in mitotic events, such as centrosome duplication, separation and maturation, and spindle formation (Willems et al, 2018). However, it also exerts some non-mitotic roles in the regulation of primary cilia formation (Bertolin and Tramier, 2020). AURKA can be phosphorylated by Human Enhancer of Filamentation 1 (HEF1, also known as NEDD9).…”