Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 06 2023
23 06 2023
Historique:
received:
08
08
2022
accepted:
05
06
2023
medline:
26
6
2023
pubmed:
24
6
2023
entrez:
23
6
2023
Statut:
epublish
Résumé
Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based 'omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.
Identifiants
pubmed: 37353488
doi: 10.1038/s41467-023-39241-7
pii: 10.1038/s41467-023-39241-7
pmc: PMC10290137
doi:
Substances chimiques
Proteome
0
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
3742Subventions
Organisme : NIA NIH HHS
ID : R01 AG067598
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG061869
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG072599
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG074004
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032969
Pays : United States
Informations de copyright
© 2023. The Author(s).
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