Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation.
Amino Acid Motifs
Amino Acid Sequence
Cell Cycle Proteins
/ metabolism
Chromosome Segregation
Feedback, Physiological
HEK293 Cells
HeLa Cells
Humans
Kinetochores
/ metabolism
Mitosis
Phosphoprotein Phosphatases
/ metabolism
Phosphorylation
Phosphoserine
/ metabolism
Protein Binding
Protein Serine-Threonine Kinases
/ metabolism
Proteins
/ chemistry
Proto-Oncogene Proteins
/ metabolism
Polo-Like Kinase 1
Apolo1
PLK1
PP1γ
chromosome segregation
kinetochore
mitosis
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
13 07 2021
13 07 2021
Historique:
received:
22
09
2019
revised:
01
04
2020
accepted:
15
06
2021
entrez:
14
7
2021
pubmed:
15
7
2021
medline:
9
2
2022
Statut:
ppublish
Résumé
Stable transmission of genetic material during cell division requires accurate chromosome segregation. PLK1 dynamics at kinetochores control establishment of correct kinetochore-microtubule attachments and subsequent silencing of the spindle checkpoint. However, the regulatory mechanism responsible for PLK1 activity in prometaphase has not yet been affirmatively identified. Here we identify Apolo1, which tunes PLK1 activity for accurate kinetochore-microtubule attachments. Apolo1 localizes to kinetochores during early mitosis, and suppression of Apolo1 results in misaligned chromosomes. Using the fluorescence resonance energy transfer (FRET)-based PLK1 activity reporter, we found that Apolo1 sustains PLK1 kinase activity at kinetochores for accurate attachment during prometaphase. Apolo1 is a cognate substrate of PLK1, and the phosphorylation enables PP1γ to inactivate PLK1 by dephosphorylation. Mechanistically, Apolo1 constitutes a bridge between kinase and phosphatase, which governs PLK1 activity in prometaphase. These findings define a previously uncharacterized feedback loop by which Apolo1 provides fine-tuning for PLK1 to guide chromosome segregation in mitosis.
Identifiants
pubmed: 34260926
pii: S2211-1247(21)00719-1
doi: 10.1016/j.celrep.2021.109343
pmc: PMC8358895
mid: NIHMS1724377
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
Proteins
0
Proto-Oncogene Proteins
0
Phosphoserine
17885-08-4
Protein Serine-Threonine Kinases
EC 2.7.11.1
Phosphoprotein Phosphatases
EC 3.1.3.16
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109343Subventions
Organisme : NCI NIH HHS
ID : R01 CA164133
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK056292
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115812
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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