Pharmacological targeting of the Hsp70 chaperone.
The molecular chaperone, heat shock protein 70 (Hsp70), acts at multiple steps in a protein's life cycle, including during the processes of folding, trafficking, remodeling and degradation. To accomplish these various tasks, the activity of Hsp70 is shaped by a host of co-chaperones, which bind to the core chaperone and influence its functions. Genetic studies have strongly linked Hsp70 and its co-chaperones to numerous diseases, including cancer, neurodegeneration and microbial pathogenesis, yet the potential of this chaperone as a therapeutic target remains largely underexplored. Here, we review the current state of Hsp70 as a drug target, with a special emphasis on the important challenges and opportunities imposed by its co-chaperones, protein-protein interactions and allostery.
Department of Pathology and the Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Srikanth
S
Patury
Yoshinari
Y
Miyata
Jason E
JE
Gestwicki
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006017:Glycolipids / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology
D004224:Diterpenes; D005419:Flavonoids; D006017:Glycolipids; D006146:Guanidines; D018840:HSP70 Heat-Shock Proteins; D011743:Pyrimidines; C011117:sulfoglycolipids; C033797:spergualin; C031049:geranylgeranylacetone