Selective targeting of the stress chaperome as a therapeutic strategy Journal Article
| Authors: | Taldone, T.; Ochiana, S. O.; Patel, P. D.; Chiosis, G. |
| Article Title: | Selective targeting of the stress chaperome as a therapeutic strategy |
| Abstract: | Normal cellular function is maintained by coordinated proteome machinery that performs a vast array of activities. Helping the proteome in such roles is the chaperome, a network of molecular chaperones and folding enzymes. The stressed cell contains, at any time, a complex mixture of chaperome complexes; a majority performs 'housekeeping functions' similarly to non-stressed, normal cells, but a finely-tuned fraction buffers the proteome altered by chronic stress. The stress chaperome is epigenetically distinct from its normal, housekeeping counterpart, providing a basis for its selective targeting by small molecules. We discuss here the development of chaperome inhibitors, and how agents targeting chaperome members in stressed cells are in fact being directed towards chaperome complexes, and their effect is therefore determined by their ability to sample and engage such complexes. A new approach is needed to target and implement chaperome modulators in the investigation of diseases, and we propose that the classical thinking in drug discovery needs adjustment when developing chaperome-targeting drugs. |
| Keywords: | controlled study; protein expression; protein phosphorylation; drug targeting; dna replication; protein function; proteome; cell function; protein degradation; protein protein interaction; protein targeting; protein binding; adenosine diphosphate; endoplasmic reticulum; dna; protein processing; drug mechanism; epigenetics; heat shock protein 90; stress; tumor necrosis factor receptor; adenosine triphosphate; protein folding; protein structure; sumoylation; cell motility; protein methylation; hsp70; radicicol; hsp90; chaperone; epigenetic regulation; ansamycin derivative; alvespimycin; buffer; molecular chaperone; chronic stress; human; article; chemical tools; hsp60; luminespib |
| Journal Title: | Trends in Pharmacological Sciences |
| Volume: | 35 |
| Issue: | 11 |
| ISSN: | 0165-6147 |
| Publisher: | Cell Press |
| Date Published: | 2014-11-01 |
| Start Page: | 592 |
| End Page: | 603 |
| Language: | English |
| DOI: | 10.1016/j.tips.2014.09.001 |
| PROVIDER: | scopus |
| PUBMED: | 25262919 |
| PMCID: | PMC4254259 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work