Structural and functional complexity of HSP90 in cellular homeostasis and disease Review
| Authors: | Chiosis, G.; Digwal, C. S.; Trepel, J. B.; Neckers, L. |
| Review Title: | Structural and functional complexity of HSP90 in cellular homeostasis and disease |
| Abstract: | Heat shock protein 90 (HSP90) is a chaperone with vital roles in regulating proteostasis, long recognized for its function in protein folding and maturation. A view is emerging that identifies HSP90 not as one protein that is structurally and functionally homogeneous but, rather, as a protein that is shaped by its environment. In this Review, we discuss evidence of multiple structural forms of HSP90 in health and disease, including homo-oligomers and hetero-oligomers, also termed epichaperomes, and examine the impact of stress, post-translational modifications and co-chaperones on their formation. We describe how these variations influence context-dependent functions of HSP90 as well as its interaction with other chaperones, co-chaperones and proteins, and how this structural complexity of HSP90 impacts and is impacted by its interaction with small molecule modulators. We close by discussing recent developments regarding the use of HSP90 inhibitors in cancer and how our new appreciation of the structural and functional heterogeneity of HSP90 invites a re-evaluation of how we discover and implement HSP90 therapeutics for disease treatment. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. |
| Journal Title: | Nature Reviews Molecular Cell Biology |
| Volume: | 24 |
| Issue: | 11 |
| ISSN: | 1471-0072 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-11-01 |
| Start Page: | 797 |
| End Page: | 815 |
| Language: | English |
| DOI: | 10.1038/s41580-023-00640-9 |
| PUBMED: | 37524848 |
| PROVIDER: | scopus |
| PMCID: | PMC10592246 |
| DOI/URL: | |
| Notes: | Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Gabriela Chiosis -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work