Chaperome heterogeneity and its implications for cancer study and treatment.
70 kilodalton heat shock protein (Hsp70)
biomarker
cancer biology
cancer therapy
chaperome
chaperone
chemical biology
chemical probes
epichaperome
heat shock protein 90 (Hsp90)
protein networks
stress response
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
08 02 2019
08 02 2019
Historique:
pubmed:
10
11
2018
medline:
27
6
2019
entrez:
10
11
2018
Statut:
ppublish
Résumé
The chaperome is the collection of proteins in the cell that carry out molecular chaperoning functions. Changes in the interaction strength between chaperome proteins lead to an assembly that is functionally and structurally distinct from each constituent member. In this review, we discuss the epichaperome, the cellular network that forms when the chaperome components of distinct chaperome machineries come together as stable, functionally integrated, multimeric complexes. In tumors, maintenance of the epichaperome network is vital for tumor survival, rendering them vulnerable to therapeutic interventions that target critical epichaperome network components. We discuss how the epichaperome empowers an approach for precision medicine cancer trials where a new target, biomarker, and relevant drug candidates can be correlated and integrated. We introduce chemical biology methods to investigate the heterogeneity of the chaperome in a given cellular context. Lastly, we discuss how ligand-protein binding kinetics are more appropriate than equilibrium binding parameters to characterize and unravel chaperome targeting in cancer and to gauge the selectivity of ligands for specific tumor-associated chaperome pools.
Identifiants
pubmed: 30409908
pii: S0021-9258(20)36860-5
doi: 10.1074/jbc.REV118.002811
pmc: PMC6369301
doi:
Substances chimiques
Antineoplastic Agents
0
Molecular Chaperones
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2162-2179Subventions
Organisme : NIAID NIH HHS
ID : R21 AI090501
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA158609
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA192937
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA155226
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA102031
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032969
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172546
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG028811
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA186866
Pays : United States
Informations de copyright
© 2019 Wang et al.
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