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. Van Hove; N. M. Levinson; G. Gasmi-Seabrook; N. Joly; M. Poteau; G. Velez-Aguilera; O. Gavet; A. Castro; M. Dasso; T. Lorca; F. Sicheri; L. Pintard

doi:10.1038/s41467-021-21922-w

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. Van Hove, N. M. Levinson, G. Gasmi-Seabrook, N. Joly, M. Poteau, G. Velez-Aguilera, O. Gavet, A. Castro, M. Dasso, T. Lorca, F. Sicheri, L. Pintard

Pharmacology

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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.

Original language	English (US)
Article number	1899
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21922-w
State	Published - Dec 1 2021

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Publisher Copyright:
© 2021, The Author(s).

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Tavernier, N., Thomas, Y., Vigneron, S., Maisonneuve, P., Orlicky, S., Mader, P., Regmi, S. G., Van Hove, L., Levinson, N. M., Gasmi-Seabrook, G., Joly, N., Poteau, M., Velez-Aguilera, G., Gavet, O., Castro, A., Dasso, M., Lorca, T., Sicheri, F., & Pintard, L. (2021). Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry. Nature communications, 12(1), Article 1899. https://doi.org/10.1038/s41467-021-21922-w

Tavernier, N, Thomas, Y, Vigneron, S, Maisonneuve, P, Orlicky, S, Mader, P, Regmi, SG, Van Hove, L, Levinson, NM, Gasmi-Seabrook, G, Joly, N, Poteau, M, Velez-Aguilera, G, Gavet, O, Castro, A, Dasso, M, Lorca, T, Sicheri, F & Pintard, L 2021, 'Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry', Nature communications, vol. 12, no. 1, 1899. https://doi.org/10.1038/s41467-021-21922-w

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AU - Thomas, Y.

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AU - Maisonneuve, P.

AU - Orlicky, S.

AU - Mader, P.

AU - Regmi, S. G.

AU - Van Hove, L.

AU - Levinson, N. M.

AU - Gasmi-Seabrook, G.

AU - Joly, N.

AU - Poteau, M.

AU - Velez-Aguilera, G.

AU - Gavet, O.

AU - Castro, A.

AU - Dasso, M.

AU - Lorca, T.

AU - Sicheri, F.

AU - Pintard, L.

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

Abstract

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