Aurora A kinase activation: Different means to different ends

Tavernier, Nicolas; Sicheri, Frank; Pintard, Lionel

doi:10.1083/jcb.202106128

Cited by 24 publications

(26 citation statements)

References 17 publications

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“…While the latter kinases are known mediators in FAK signaling pathways, such a connection has not been reported for Aurora A. The regulation of Aurora A is complex and several different activation mechanisms have been elucidated [46], including binding to Ser112phosphorylated Bora, autophosphorylation at Thr288 after interactions with Tpx2, and transphosphorylation after interactions with Cep192 [47]; furthermore, PAK1 was shown to promote Aurora A Thr288 phosphorylation [48]. Thus, further investigations are needed to clarify how FAK regulates PLK1 activity, possibly via Aurora A.…”

Section: Discussionmentioning

confidence: 99%

Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis

Kamranvar

Gupta

Wasberg

et al. 2022

Cells

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Integrin-mediated adhesion to the extracellular matrix is a key regulator of the cell cycle, as demonstrated for the passage of the G1/S checkpoint and the completion of cytokinetic abscission. Here, integrin-dependent regulation of the cell cycle in G2 and early M phases was investigated. The progression through the G2 and M phases was monitored by live-cell imaging and immunofluorescence staining in adherent and non-adherent fibroblast cells. Non-adherent cells, as well as adherent cells lacking FAK activity due to suppressed expression or pharmacological inhibition, exhibited a prolonged G2 phase and severely defect centrosome separation, resulting in delayed progress through the early mitotic stages. The activation of the critical mitotic regulator PLK1 and its indirect target Eg5, a kinesin-family motor protein driving the centrosome separation, were reduced in the cells lacking FAK activity. Furthermore, the absence of integrin adhesion or FAK activity destabilized the structural integrity of centrosomes and often caused detachment of pericentriolar material from the centrioles. These data identify a novel adhesion-dependent mechanism by which integrins via FAK and PLK1 contribute to the regulation of the cell cycle in the G2 and early M phases, and to the maintenance of genome integrity.

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Section: Discussionmentioning

confidence: 99%

Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis

Kamranvar

Gupta

Wasberg

et al. 2022

Cells

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“…The mechanisms involved in the spatio-temporal regulation of Aurora-A rely on the binding of co-factors that allosterically regulate Aurora-A, either inducing (CEP192, TPX2 and Ajuba), or not (Bora), its auto-phosphorylation on threonine 288 (Thr288), a residue positioned within the activation loop that is generally associated with the enhancement of its kinase activity [ 77 , 78 , 79 , 80 , 81 ]. Nevertheless, in some cases the phosphorylation on Thr288 is necessary but not sufficient to fully activate Aurora-A [ 82 ]. Indeed, phosphorylation, acetylation and SUMOylation on alternative residues by other enzymes are important to regulate Aurora-A activity and functions [ 61 , 83 , 84 , 85 , 86 , 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

PARP10 Mediates Mono-ADP-Ribosylation of Aurora-A Regulating G2/M Transition of the Cell Cycle

Paola

Barretta

Dathan

et al. 2022

Cancers

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Intracellular mono-ADP-ribosyltransferases (mono-ARTs) catalyze the covalent attachment of a single ADP-ribose molecule to protein substrates, thus regulating their functions. PARP10 is a soluble mono-ART involved in the modulation of intracellular signaling, metabolism and apoptosis. PARP10 also participates in the regulation of the G1- and S-phase of the cell cycle. However, the role of this enzyme in G2/M progression is not defined. In this study, we found that genetic ablation, protein depletion and pharmacological inhibition of PARP10 cause a delay in the G2/M transition of the cell cycle. Moreover, we found that the mitotic kinase Aurora-A, a previously identified PARP10 substrate, is actively mono-ADP-ribosylated (MARylated) during G2/M transition in a PARP10-dependent manner. Notably, we showed that PARP10-mediated MARylation of Aurora-A enhances the activity of the kinase in vitro. Consistent with an impairment in the endogenous activity of Aurora-A, cells lacking PARP10 show a decreased localization of the kinase on the centrosomes and mitotic spindle during G2/M progression. Taken together, our data provide the first evidence of a direct role played by PARP10 in the progression of G2 and mitosis, an event that is strictly correlated to the endogenous MARylation of Aurora-A, thus proposing a novel mechanism for the modulation of Aurora-A kinase activity.

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“…PLK1 activity is known to be controlled by phosphorylation at Thr210 in the activation loop by Aurora A ( Gheghiani L et al, 2017 ; Raab M et al, 2022 ), and additional PLK1 modifications have been reported, which may further contribute to its spatiotemporal regulation ( Caron D et al, 2016 ; Liu X et al, 2016 ; Yang X et al, 2017 ). Also, the regulation of Aurora A is complex, and several different activation mechanisms have been elucidated ( Zhao Z S et al, 2005 ; Tavernier N et al, 2021 ). Thus, while the mechanism by which FAK promotes PLK1 activity remains to be identified, it is likely to act in parallel with or possibly upstream of Aurora A.…”

Section: Spindle Formationmentioning

confidence: 99%

Contribution of integrin adhesion to cytokinetic abscission and genomic integrity

Rani

Gupta

Johansson

et al. 2022

Front. Cell Dev. Biol.

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Recent research shows that integrin-mediated adhesion contributes to the regulation of cell division at two key steps: the formation of the mitotic spindle at the mitotic entry and the final cytokinetic abscission at the mitotic exit. Failure in either of these processes will have a direct impact on the other in each round of the cell cycle and on the genomic integrity. This review aims to present how integrin signals are involved at these cell cycle stages under normal conditions and some safety mechanisms that may counteract the generation of aneuploid cells in cases of defective integrin signals.

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Aurora A kinase activation: Different means to different ends

Cited by 24 publications

References 17 publications

Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis

Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis

PARP10 Mediates Mono-ADP-Ribosylation of Aurora-A Regulating G2/M Transition of the Cell Cycle

Contribution of integrin adhesion to cytokinetic abscission and genomic integrity

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