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Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry

N. Tavernier, Y. Thomas, S. Vigneron, P. Maisonneuve, S. Orlicky, P. Mader, S. G. Regmi, L. Hove, N. M. Levinson, G. Gasmi-Seabrook, N. Joly, M. Poteau, G. Velez-Aguilera, O. Gavet, A. Castro, M. Dasso, T. Lorca, F. Sicheri () and L. Pintard ()
Additional contact information
N. Tavernier: Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Sinai Health System
Y. Thomas: Programme équipe Labellisée Ligue Contre le Cancer, Institut Jacques Monod, UMR7592, Université de Paris, CNRS
S. Vigneron: Centre de Recherche de Biologie cellulaire de Montpellier, UMR 5237, Université de Montpellier, CNRS
P. Maisonneuve: Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Sinai Health System
S. Orlicky: Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Sinai Health System
P. Mader: Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Sinai Health System
S. G. Regmi: Eunice Kennedy Shriver National Institute of Child Health and Human Development
L. Hove: Programme équipe Labellisée Ligue Contre le Cancer, Institut Jacques Monod, UMR7592, Université de Paris, CNRS
N. M. Levinson: University of Minnesota
G. Gasmi-Seabrook: Princess Margaret Cancer Centre, University Health Network
N. Joly: Programme équipe Labellisée Ligue Contre le Cancer, Institut Jacques Monod, UMR7592, Université de Paris, CNRS
M. Poteau: Institut Gustave Roussy CNRS UMR9019
G. Velez-Aguilera: Programme équipe Labellisée Ligue Contre le Cancer, Institut Jacques Monod, UMR7592, Université de Paris, CNRS
O. Gavet: Institut Gustave Roussy CNRS UMR9019
A. Castro: Centre de Recherche de Biologie cellulaire de Montpellier, UMR 5237, Université de Montpellier, CNRS
M. Dasso: Eunice Kennedy Shriver National Institute of Child Health and Human Development
T. Lorca: Centre de Recherche de Biologie cellulaire de Montpellier, UMR 5237, Université de Montpellier, CNRS
F. Sicheri: Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Sinai Health System
L. Pintard: Programme équipe Labellisée Ligue Contre le Cancer, Institut Jacques Monod, UMR7592, Université de Paris, CNRS

Nature Communications, 2021, vol. 12, issue 1, 1-22

Abstract: Abstract Polo-like kinase 1 (Plk1) is instrumental for mitotic entry and progression. Plk1 is activated by phosphorylation on a conserved residue Thr210 in its activation segment by the Aurora A kinase (AURKA), a reaction that critically requires the co-factor Bora phosphorylated by a CyclinA/B-Cdk1 kinase. Here we show that phospho-Bora is a direct activator of AURKA kinase activity. We localize the key determinants of phospho-Bora function to a 100 amino acid region encompassing two short Tpx2-like motifs and a phosphoSerine-Proline motif at Serine 112, through which Bora binds AURKA. The latter substitutes in trans for the Thr288 phospho-regulatory site of AURKA, which is essential for an active conformation of the kinase domain. We demonstrate the importance of these determinants for Bora function in mitotic entry both in Xenopus egg extracts and in human cells. Our findings unveil the activation mechanism of AURKA that is critical for mitotic entry.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21922-w

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DOI: 10.1038/s41467-021-21922-w

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