Srikanth Patury, Yoshinari Miyata and Jason E. Gestwicki Pages 1337 - 1351 ( 15 )
The molecular chaperone, heat shock protein 70 (Hsp70), acts at multiple steps in a proteins 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.
Proteostasis, flavonoids, dihydropyrimidines, spergualin, sulfoglycolipids, geranylgeranyl acetone, protein folding, ATPase, protein-protein interactions
University of Michigan, Life Sciences Institute, 210 Washtenaw Ave, Ann Arbor, MI 48109-2216.