The therapeutic potential of targeting Hsp90-Cdc37 interactions in several diseases

• Published in: Current drug targets
• Main Authors: Zhang, Xuerong, Li, Shehan, Li, Zibo, Cheng, Liangkai, Liu, Zhongqiu, Wang, Caiyan
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.08.2022
• Subjects: cell division cycle 37; diseases; protein-protein interaction; inhibitor; Heat shock protein 90
• ISSN: 1873-5592
• DOI: 10.2174/1389450123666220408101544

Heat shock protein (Hsp) 90 is an ATP-dependent chaperone and plays a vital role in the folding, maturation, and stability of protein. Hsp90 and its client proteins have become targets of various diseases through the regulation of disease-related proteins. Inhibition of Hsp90 production and activity prevent ATP hydrolysis, resulting in the ubiquitination and proteasome degradation of client proteins. However, Hsp90 inhibitor has obvious toxic side effects and the inevitable heat shock response. Cell division cycle 37 (Cdc37) is a crucial Hsp90 co-chaperone and have protein kinase-specific, which forms complex with Hsp90 to regulate kinase and non-kinase client's activities, cell communication and signal transduction. Hsp90-Cdc37 complex maintains cell survival by stabilizing abnormal client proteins and regulating cell growth signals. The abnormal activation of Hsp90-Cdc37 protein-protein interaction (PPI) often leads to aggravation of diseases, such as cancer and neurodegenerative diseases. Compared with ATP competitive Hsp90 inhibitors, blocking Hsp90-Cdc37 PPI has higher selectivity, fewer toxic side effects and better application prospects. This review detailed the biological characteristics of Hsp90-Cdc37 PPI and its role in several human diseases. Besides, the latest research progress of inhibitors is summarized and discussed to guide further research and clinical application.