HSP90-CDC37-PP5 forms a structural platform for kinase ... - Nature
Nov 29, 2022 · Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the...
Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein …
Sep 18, 2019 · Disrupting the interactions between Hsp90 and Cdc37 is emerging as an alternative and specific way to regulate the Hsp90 chaperone cycle in a manner not involving adenosine triphosphatase inhibition. Here, we identified DDO-5936 as a small-molecule inhibitor of the Hsp90-Cdc37 protein-protein interaction (PPI) in colorectal cancer.
Targeting the Hsp90-Cdc37-client protein interaction to disrupt Hsp90 …
Apr 27, 2018 · Silencing Cdc37 using shRNA disrupts the Hsp90 chaperone machinery via impairing the association of client protein with Hsp90 and prevents protein maturation, which may subsequently induce a proteasomal degradation of client proteins, and finally suppresses the proliferation of human colon cancer cells . Additionally, depletion of Cdc37 could ...
Structural dynamics of RAF1-HSP90-CDC37 and ... - Nature
Mar 2, 2024 · CDC37 facilitates client protein recruitment to HSP90 by interacting with the client and HSP90 to aid their association 14,15.
Hsp90 provides a platform for kinase dephosphorylation by PP5
Apr 17, 2023 · We set out to understand how Hsp90 activates PP5, and how Hsp90 can help position PP5 for efficient client dephosphorylation. Our Hsp90:Cdc37:CRaf KD:PP5 complex structure illustrates the...
Targeting the Hsp90-Cdc37-client protein interaction to
Apr 27, 2018 · 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.
HSP90-CDC37-PP5 forms a structural platform for kinase ...
Nov 29, 2022 · Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of regulatory phosphorylation from client kinases and their release from the HSP90-CDC …
Targeting the HSP90–CDC37–kinase chaperone cycle: A promising ...
Apr 12, 2021 · The ATP binding process induces HSP90 to move from an open to a closed conformation, while CDC37 binding to the HSP90 NTD competitively inhibits this ATP binding process. The middle domain (MD) of HSP90 (amino acids 262–524) is implicated in the binding of client proteins and cochaperones.
Assembly mechanism of early Hsp90-Cdc37-kinase complexes
Mar 16, 2022 · Here, we investigate how protein kinases are recruited and loaded to the Hsp90-Cdc37 complex, the first step during Hsp90-mediated chaperoning that leads to enhanced client kinase stability and activation. We show that conformational dynamics of all partners is a critical feature of the underlying loading mechanism.
Hsp90·Cdc37 Complexes with Protein Kinases Form …
Dec 25, 2015 · Protein kinases are the most prominent group of heat shock protein 90 (Hsp90) clients and are recruited to the molecular chaperone by the kinase-specific cochaperone cell division cycle 37 (Cdc37). The interaction between Hsp90 and nematode Cdc37 is mediated by binding of the Hsp90 middle domain to an N-terminal region of Caenorhabditis elegans ...