A dimerization-dependent mechanism regulates enzymatic activation and nuclear entry of PLK1.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
28
06
2021
accepted:
22
10
2021
revised:
18
10
2021
pubmed:
12
11
2021
medline:
17
2
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
Polo-like kinase 1 (PLK1) is a crucial regulator of cell cycle progression. It is established that the activation of PLK1 depends on the coordinated action of Aurora-A and Bora. Nevertheless, very little is known about the spatiotemporal regulation of PLK1 during G2, specifically, the mechanisms that keep cytoplasmic PLK1 inactive until shortly before mitosis onset. Here, we describe PLK1 dimerization as a new mechanism that controls PLK1 activation. During the early G2 phase, Bora supports transient PLK1 dimerization, thus fine-tuning the timely regulated activation of PLK1 and modulating its nuclear entry. At late G2, the phosphorylation of T210 by Aurora-A triggers dimer dissociation and generates active PLK1 monomers that support entry into mitosis. Interfering with this critical PLK1 dimer/monomer switch prevents the association of PLK1 with importins, limiting its nuclear shuttling, and causes nuclear PLK1 mislocalization during the G2-M transition. Our results suggest a novel conformational space for the design of a new generation of PLK1 inhibitors.
Identifiants
pubmed: 34759346
doi: 10.1038/s41388-021-02094-9
pii: 10.1038/s41388-021-02094-9
pmc: PMC8755526
doi:
Substances chimiques
Cell Cycle Proteins
0
Proto-Oncogene Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
372-386Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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