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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.

SUBMITTER: Wang T

PROVIDER: S-EPMC6369301 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Chaperome heterogeneity and its implications for cancer study and treatment.

Wang Tai T Rodina Anna A Dunphy Mark P MP Corben Adriana A Modi Shanu S Guzman Monica L ML Gewirth Daniel T DT Chiosis Gabriela G

The Journal of biological chemistry 20181108 6

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 ...[more]

PMID: 30409908

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Dataset Information

Chaperome heterogeneity and its implications for cancer study and treatment.

Publications

Chaperome heterogeneity and its implications for cancer study and treatment.

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