A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
30
09
2022
accepted:
26
05
2023
medline:
26
7
2023
pubmed:
23
6
2023
entrez:
22
6
2023
Statut:
ppublish
Résumé
Redox metabolites have been observed to fluctuate through the cell cycle in cancer cells, but the functional impacts of such metabolic oscillations remain unknown. Here, we uncover a mitosis-specific nicotinamide adenine dinucleotide phosphate (NADPH) upsurge that is essential for tumour progression. Specifically, NADPH is produced by glucose 6-phosphate dehydrogenase (G6PD) upon mitotic entry, which neutralizes elevated reactive oxygen species (ROS) and prevents ROS-mediated inactivation of mitotic kinases and chromosome missegregation. Mitotic activation of G6PD depends on the phosphorylation of its co-chaperone protein BAG3 at threonine 285, which results in dissociation of inhibitory BAG3. Blocking BAG3
Identifiants
pubmed: 37349486
doi: 10.1038/s42255-023-00832-9
pii: 10.1038/s42255-023-00832-9
doi:
Substances chimiques
NADP
53-59-8
Reactive Oxygen Species
0
BAG3 protein, human
0
Adaptor Proteins, Signal Transducing
0
Apoptosis Regulatory Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1141-1158Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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