Hsp90-mediated regulation of DYRK3 couples stress granule disassembly and growth via mTORC1 signaling.
DYRK3
FUS-ALS
Hsp90
phase separation
stress granules
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
revised:
02
02
2021
received:
17
09
2020
accepted:
19
02
2021
pubmed:
20
3
2021
medline:
3
6
2021
entrez:
19
3
2021
Statut:
ppublish
Résumé
Stress granules (SGs) are dynamic condensates associated with protein misfolding diseases. They sequester stalled mRNAs and signaling factors, such as the mTORC1 subunit raptor, suggesting that SGs coordinate cell growth during and after stress. However, the molecular mechanisms linking SG dynamics and signaling remain undefined. We report that the chaperone Hsp90 is required for SG dissolution. Hsp90 binds and stabilizes the dual-specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3) in the cytosol. Upon Hsp90 inhibition, DYRK3 dissociates from Hsp90 and becomes inactive. Inactive DYRK3 is subjected to two different fates: it either partitions into SGs, where it is protected from irreversible aggregation, or it is degraded. In the presence of Hsp90, DYRK3 is active and promotes SG disassembly, restoring mTORC1 signaling and translation. Thus, Hsp90 links stress adaptation and cell growth by regulating the activity of a key kinase involved in condensate disassembly and translation restoration.
Identifiants
pubmed: 33738926
doi: 10.15252/embr.202051740
pmc: PMC8097338
doi:
Substances chimiques
RNA, Messenger
0
Mechanistic Target of Rapamycin Complex 1
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
e51740Subventions
Organisme : European Research Council
ID : ERC-StG2013 337713
Pays : International
Organisme : European Research Council (ERC)
ID : 725836
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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