Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 Oct 2024
16 Oct 2024
Historique:
received:
16
03
2024
accepted:
04
10
2024
medline:
17
10
2024
pubmed:
17
10
2024
entrez:
16
10
2024
Statut:
epublish
Résumé
The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data demonstrate that phosphorylation of these serine residues enhances HSP90's interactions with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Moreover, we establish a direct link between epichaperome function and cellular physiology, particularly in contexts where robust proliferation and adaptive behavior are essential, such as in cancer and pluripotent stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone assemblies in diseases characterized by epichaperome dysregulation, thereby bridging the gap between fundamental research and precision medicine.
Identifiants
pubmed: 39414766
doi: 10.1038/s41467-024-53178-5
pii: 10.1038/s41467-024-53178-5
doi:
Substances chimiques
HSP90 Heat-Shock Proteins
0
Molecular Chaperones
0
Serine
452VLY9402
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8912Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R01 CA172546; P01 CA186866
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R56 AG061869, R01 AG067598, R01 AG074004, R01 AG072599, R56 AG072599, RF1 AG071805
Informations de copyright
© 2024. The Author(s).
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