Abstract
Heat shock protein 90 (Hsp90) is a critical molecular chaperone protein that regulates the folding, maturation, and stability of a wide variety of proteins. In recent years, the development of Hsp90-directed inhibitors has grown rapidly, and many of these inhibitors have entered clinical trials. In parallel, the functional dissection of the Hsp90 chaperone machinery has highlighted the activity disruption of Hsp90 co-chaperone as a potential target. With the roles of Hsp90 co-chaperones being elucidated, cell division cycle 37 (Cdc37), a ubiquitous co-chaperone of Hsp90 that directs the selective client proteins into the Hsp90 chaperone cycle, shows great promise. Moreover, the Hsp90-Cdc37-client interaction contributes to the regulation of cellular response and cellular growth and is more essential to tumor tissues than normal tissues. Herein, we discuss the current understanding of the clients of Hsp90-Cdc37, the interaction of Hsp90-Cdc37-client protein, and the therapeutic possibilities of targeting Hsp90-Cdc37-client protein interaction as a strategy to inhibit Hsp90 chaperone machinery to present new insights on alternative ways of inhibiting Hsp90 chaperone machinery.
Highlights
Heat shock protein 90 (Hsp90) is a critically conserved protein and one of the major molecular chaperones within eukaryotic cells [1]
We discuss the current understanding of the clients of Hsp90-cell division cycle 37 (Cdc37), the interaction of Hsp90Cdc37-client, and the prospects of targeting Hsp90Cdc37-client interaction as a target for therapeutic intervention of the Hsp90 chaperone machinery
Dephosphorylation is important for the reversal of Cdc37’s resistance to nonspecific phosphatases and constitutive phosphorylation [48, 65]. These results show the regulatory mechanisms of Cdc37 activity and the molecular basis for the ability of casein kinase 2 (CK2) and phosphatase 5 (PP5) to regulate cellular functions of the Cdc37-client protein complex
Summary
Heat shock protein 90 (Hsp90) is a critically conserved protein and one of the major molecular chaperones within eukaryotic cells [1]. Hsp client proteins originate from distinct functional classes, including transcription factors (e.g., HIF1α, ATF3, and p53), steroid hormone receptors (e.g., estrogen receptor, glucocorticoid receptor, and progesterone receptor), and kinases (e.g., EGFR, B-raf, and SRC). Many of these client proteins are commonly overexpressed and/or frequently mutated in cancer cells [5,6,7]. Proper phosphoserine of Cdc at Ser is necessary for Hsp chaperone machinery to recognize the structural perturbation at the client protein domain and helps Cdc to stabilize its own structure and participate in the interaction with Hsp90 [27] These works have heightened the understanding of the phosphorylation on Cdc37’s conformation and ability to bind to Hsp. CHUK, MAP3K7, EIF2AK2, MAP3K14, MAP3K1, PRKCQ, PRKCB, MAP3K3, PRKCZ, SRC, TGFBR1, MAP3K11, AKT1, ACVR1, IRAK1, TBK1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
