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Systems level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation

ABSTRACT: There is a penury of regents and methods that enable the identification, analysis, and modulation of context-specific protein-protein interaction (PPI) network dysfunctions in native (unengineered) cells and tissues. Herein, we take advantage of first-in-class 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

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr. Thomas A. Neubert Dr. Gabriela Chiosis

PROVIDER: MSV000087540 | MassIVE | Fri May 28 13:54:00 BST 2021

SECONDARY ACCESSION(S): PXD042262

REPOSITORIES: MassIVE

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