An mTORC1-to-CDK1 Switch Maintains Autophagy Suppression during Mitosis.
A549 Cells
Autophagy
/ physiology
CDC2 Protein Kinase
/ metabolism
Cell Line
Cell Line, Tumor
Female
HCT116 Cells
HEK293 Cells
HT29 Cells
HeLa Cells
Humans
Lysosomes
/ metabolism
Male
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Mitosis
/ physiology
Phosphorylation
/ physiology
Signal Transduction
/ physiology
ATG13
ATG14
CDK1
RAPTOR
TFEB
ULK1
autophagy
mTOR
mitosis
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
16 01 2020
16 01 2020
Historique:
received:
16
02
2019
revised:
19
07
2019
accepted:
10
10
2019
pubmed:
18
11
2019
medline:
1
4
2020
entrez:
18
11
2019
Statut:
ppublish
Résumé
Since nuclear envelope breakdown occurs during mitosis in metazoan cells, it has been proposed that macroautophagy must be inhibited to maintain genome integrity. However, repression of macroautophagy during mitosis remains controversial and mechanistic detail limited to the suggestion that CDK1 phosphorylates VPS34. Here, we show that initiation of macroautophagy, measured by the translocation of the ULK complex to autophagic puncta, is repressed during mitosis, even when mTORC1 is inhibited. Indeed, mTORC1 is inactive during mitosis, reflecting its failure to localize to lysosomes due to CDK1-dependent RAPTOR phosphorylation. While mTORC1 normally represses autophagy via phosphorylation of ULK1, ATG13, ATG14, and TFEB, we show that the mitotic phosphorylation of these autophagy regulators, including at known repressive sites, is dependent on CDK1 but independent of mTOR. Thus, CDK1 substitutes for inhibited mTORC1 as the master regulator of macroautophagy during mitosis, uncoupling autophagy regulation from nutrient status to ensure repression of macroautophagy during mitosis.
Identifiants
pubmed: 31733992
pii: S1097-2765(19)30794-4
doi: 10.1016/j.molcel.2019.10.016
pmc: PMC6964153
pii:
doi:
Substances chimiques
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
228-240.e7Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K019155/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0413
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0417
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.
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