Heat shock protein 90: its inhibition and function. (4th December 2017)

• Record Type: Journal Article
• Authors: Zuehlke, Abbey D.; Moses, Michael A.; Neckers, Len
• Is Part Of: Philosophical transactions. Volume 373:Number 1738(2018)
• Publication Date: 2017-12-04
• Subjects: molecular chaperones -- drug development -- Heat Shock Protein 90; Biology -- Periodicals; Science -- Periodicals; 570
• DOI: 10.1098/rstb.2016.0527
• Languages: English
• ISSNs: 0962-8436

Abstract

Abstract : The molecular chaperone heat shock protein 90 (Hsp90) facilitates metastable protein maturation, stabilization of aggregation-prone proteins, quality control of misfolded proteins and assists in keeping proteins in activation-competent conformations. Proteins that rely on Hsp90 for function are delivered to Hsp90 utilizing a co-chaperone–assisted cycle. Co-chaperones play a role in client transfer to Hsp90, Hsp90 ATPase regulation and stabilization of various Hsp90 conformational states. Many of the proteins chaperoned by Hsp90 (Hsp90 clients) are essential for the progression of various diseases, including cancer, Alzheimer's disease and other neurodegenerative diseases, as well as viral and bacterial infections. Given the importance of these clients in different diseases and their dynamic interplay with the chaperone machinery, it has been suggested that targeting Hsp90 and its respective co-chaperones may be an effective method for combating a large range of illnesses. This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.