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

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

Authors:	Rodina, A.; Xu, C.; Digwal, C. S.; Joshi, S.; Patel, Y.; Santhaseela, A. R.; Bay, S.; Merugu, S.; Alam, A.; Yan, P.; Yang, C.; Roychowdhury, T.; Panchal, P.; Shrestha, L.; Kang, Y.; Sharma, S.; Almodovar, J.; Corben, A.; Alpaugh, M. L.; Modi, S.; Guzman, M. L.; Fei, T.; Taldone, T.; Ginsberg, S. D.; Erdjument-Bromage, H.; Neubert, T. A.; Manova-Todorova, K.; Tsou, M. F. B.; Young, J. C.; Wang, T.; Chiosis, G.
Article Title:	Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation
Abstract:	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. © 2023, The Author(s).
Keywords:	genetics; neoplasm; neoplasms; proteome; metabolism; protein protein interaction; protein; fitness; protein interaction mapping; cell; adaptation; protein interaction maps; cell component; cancer; humans; human; acclimatization
Journal Title:	Nature Communications
Volume:	14
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2023-06-23
Start Page:	3742
Language:	English
DOI:	10.1038/s41467-023-39241-7
PUBMED:	37353488
PROVIDER:	scopus
PMCID:	PMC10290137
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85162795046&doi=10.1038%2fs41467-023-39241-7&partnerID=40&md5=35e1c8bd50dde96db4550210d46a4a5d
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors is Gabriela Chiosis -- Source: Scopus