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Review
. 2022 Sep;12(9):220134.
doi: 10.1098/rsob.220134. Epub 2022 Sep 7.

Regulating the regulator: a survey of mechanisms from transcription to translation controlling expression of mammalian cell cycle kinase Aurora A

Affiliations
Review

Regulating the regulator: a survey of mechanisms from transcription to translation controlling expression of mammalian cell cycle kinase Aurora A

Roberta Cacioppo et al. Open Biol. 2022 Sep.

Abstract

Aurora Kinase A (AURKA) is a positive regulator of mitosis with a strict cell cycle-dependent expression pattern. Recently, novel oncogenic roles of AURKA have been uncovered that are independent of the kinase activity and act within multiple signalling pathways, including cell proliferation, survival and cancer stem cell phenotypes. For this, cellular abundance of AURKA protein is per se crucial and must be tightly fine-tuned. Indeed, AURKA is found overexpressed in different cancers, typically as a result of gene amplification or enhanced transcription. It has however become clear that impaired processing, decay and translation of AURKA mRNA can also offer the basis for altered AURKA levels. Accordingly, the involvement of gene expression mechanisms controlling AURKA expression in human diseases is increasingly recognized and calls for much more research. Here, we explore and create an integrated view of the molecular processes regulating AURKA expression at the level of transcription, post-transcription and translation, intercalating discussion on how impaired regulation underlies disease. Given that targeting AURKA levels might affect more functions compared to inhibiting the kinase activity, deeper understanding of its gene expression may aid the design of alternative and therapeutically more successful ways of suppressing the AURKA oncogene.

Keywords: Aurora Kinase A; cell cycle; mRNA processing; oncogene; transcription; translation.

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Conflict of interest statement

We declare we have no competing interests.

Figures

Figure 1.
Figure 1.
Key regulators of AURKA transcription. ATR, AT-rich region. CDE, cell cycle-dependent element. CHR, cell cycle gene homology region. E-box, enhancer box. HRE, hypoxia response element. PRE, positive regulatory element. G0, G1, S, G2, M, cell cycle phases. *, factors that also interact with AURKA protein in potential regulatory feedback loops. Thick arrow indicates start site and direction of transcription. Figure created using BioRender.com.
Figure 2.
Figure 2.
Post-transcriptional regulation of AURKA mRNA. (a) Annotated 5′UTR splicing isoforms. (b) Regulators of AURKA mRNA translation (green) and decay (blue). I–IV, exons. An, polyA tail. ATG, start codon. CDS, coding sequence. m7G, 7-methyl-guanosine. miRISC, miRNA-induced silencing complex. PAS, polyadenylation site. UTR, untranslated region. Figure created using BioRender.com.
Figure 3.
Figure 3.
Different stages of gene expression integrate into AURKA temporal expression. Activation of AURKA transcription and protein degradation are likely the drivers of the respective increase and decrease in AURKA protein levels during the cell cycle. Control of mRNA stabilization also contributes to AURKA expression pattern, whereas the precise timing and extent of AURKA translational activation and translational inhibition are not yet clear. Figure created using BioRender.com.

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