Chaperome heterogeneity and its implications for cancer study and treatment Journal Article


Authors: Wang, T.; Rodina, A.; Dunphy, M. P.; Corben, A.; Modi, S.; Guzman, M. L.; Gewirth, D. T.; Chiosis, G.
Article Title: Chaperome heterogeneity and its implications for cancer study and treatment
Abstract: 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. © 2019 Wang et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: proteins; protein binding; tumors; ligands; biochemistry; diseases; machinery; chemical biology; therapeutic intervention; cellular contexts; drug candidates; cellular network; equilibrium binding; interaction strength
Journal Title: Journal of Biological Chemistry
Volume: 294
Issue: 6
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2019-02-08
Start Page: 2162
End Page: 2179
Language: English
DOI: 10.1074/jbc.REV118.002811
PUBMED: 30409908
PROVIDER: scopus
PMCID: PMC6369301
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Mark Phillip Dunphy
    49 Dunphy
  2. Shanu Modi
    134 Modi
  3. Gabriela Chiosis
    218 Chiosis
  4. Tai   Wang
    7 Wang