Epichaperomes as a gateway to understanding, diagnosing, and treating disease through rebalancing protein-protein interaction networks Book Section
| Authors: | Digwal, C. S.; Sharma, S.; Santhaseela, A. R.; Ginsberg, S. D.; Chiosis, G. |
| Editors: | Kostic, M.; Jones, L. H. |
| Article/Chapter Title: | Epichaperomes as a gateway to understanding, diagnosing, and treating disease through rebalancing protein-protein interaction networks |
| Abstract: | Alterations in proteostasis are known contributors to various maladies including cancer and neurodegenerative disorders. Here, we discuss how chemical biology has brought to proteostasis an appreciation that goes beyond biogenesis, folding, trafficking, and degradation of proteins, to incorporate the study of the interaction fate of proteins, especially as they occur in disease processes at the proteome-wide level. This has been enabled by the discovery of epichaperomes, long-lived assemblies, and disease-associated pathologic scaffolds composed of tightly bound chaperones, co-chaperones, and other factors, and catalyzed by generation and implementation of several chemical probes, from epichaperome disrupters to epichaperome affinity-purification tools and epichaperome detection and quantitation probes. We highlight the knowledge gained to date through chemical biology on the deleterious effect epichaperomes have on reshaping protein-protein interaction networks (i.e. interactomes) at a proteome-wide level in disease, especially in cancer and neurodegenerative diseases. We also discuss the restorative effects of epichaperome disrupters through rebalancing proteome-wide interactome defects. Lastly, we highlight how through the use of chemical probes to enable epichaperome detection and quantitation, the discipline of chemical biology has provided opportunities for precision medicine. © 2023 John Wiley & Sons, Inc. |
| Keywords: | neurodegeneration; cancer; companion diagnostics; precision medicine; protein-protein interaction networks; proteostasis; kinetic selectivity; epichaperomes; epichaperomics; epichaperome chemical probes; protein-connectivity dysfunction |
| Book Title: | Protein Homeostasis in Drug Discovery: A Chemical Biology Perspective |
| ISBN: | 9781119774129 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-01-01 |
| Start Page: | 3 |
| End Page: | 26 |
| Language: | English |
| DOI: | 10.1002/9781119774198.ch1 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Book Chapter: 1 -- This chapter is published under "Section I: Protein Folding and Quality Control in Drug Discovery" -- MSK author Anand Santha Seela's last name is incorrectly spelled in the publication -- Export Date: 1 March 2023 -- Source: Scopus |
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