Title:The Therapeutic Potential of Targeting Hsp90-Cdc37 Interactions in
Several Diseases
Volume: 23
Issue: 10
关键词:
热休克蛋白 90，细胞分裂周期 37，蛋白质-蛋白质相互作用，疾病，抑制剂，体内平衡。
摘要: Heat shock protein (Hsp) 90 is an ATP-dependent chaperone and plays a vital role in the
folding, maturation, and stability of a 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 prevents ATP hydrolysis, resulting in the ubiquitination and proteasome degradation of
client proteins. However, the Hsp90 inhibitor has obvious toxic side effects and the inevitable heat
shock response. Cell division cycle 37 (Cdc37) is a crucial Hsp90 kinase-specific co-chaperone,
which forms a complex with Hsp90 to regulate kinase and non-kinase client’s activities, cell communication,
and signal transduction. The 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 the 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 in inhibitors is summarized and discussed to guide further research and clinical
application.
