Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry.
Amino Acid Motifs
/ genetics
Animals
Aurora Kinase A
/ genetics
Cell Cycle Proteins
/ genetics
Cell Line, Tumor
Cyclin A2
/ genetics
Cyclin-Dependent Kinase 2
/ genetics
Enzyme Activation
Female
Humans
Mitosis
Oocytes
/ metabolism
Phosphorylation
Proline
/ genetics
Protein Serine-Threonine Kinases
/ genetics
Proto-Oncogene Proteins
/ genetics
Serine
/ genetics
Threonine
/ genetics
Xenopus laevis
Polo-Like Kinase 1
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 03 2021
26 03 2021
Historique:
received:
16
07
2020
accepted:
19
02
2021
entrez:
27
3
2021
pubmed:
28
3
2021
medline:
13
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33771996
doi: 10.1038/s41467-021-21922-w
pii: 10.1038/s41467-021-21922-w
pmc: PMC7997955
doi:
Substances chimiques
Cell Cycle Proteins
0
Cyclin A2
0
Proto-Oncogene Proteins
0
bora protein, human
0
Threonine
2ZD004190S
Serine
452VLY9402
Proline
9DLQ4CIU6V
Aurora Kinase A
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
CDK2 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 2
EC 2.7.11.22
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1899Subventions
Organisme : NCI NIH HHS
ID : R33 CA246363
Pays : United States
Organisme : CIHR
ID : MFE 152464
Pays : Canada
Organisme : CIHR
ID : FRN 414829
Pays : Canada
Organisme : CIHR
ID : FDN 143277
Pays : Canada
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