Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.

Cell | 2012

HSP90 is a molecular chaperone that associates with numerous substrate proteins called clients. It plays many important roles in human biology and medicine, but determinants of client recognition by HSP90 have remained frustratingly elusive. We systematically and quantitatively surveyed most human kinases, transcription factors, and E3 ligases for interaction with HSP90 and its cochaperone CDC37. Unexpectedly, many more kinases than transcription factors bound HSP90. CDC37 interacted with kinases, but not with transcription factors or E3 ligases. HSP90::kinase interactions varied continuously over a 100-fold range and provided a platform to study client protein recognition. In wild-type clients, HSP90 did not bind particular sequence motifs, but rather associated with intrinsically unstable kinases. Stabilization of the kinase in either its active or inactive conformation with diverse small molecules decreased HSP90 association. Our results establish HSP90 client recognition as a combinatorial process: CDC37 provides recognition of the kinase family, whereas thermodynamic parameters determine client binding within the family.

Pubmed ID: 22939624 RIS Download

Research resources used in this publication

None found

Additional research tools detected in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: NIDCR NIH HHS, United States
    Id: UL1-DE019585
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIDCR NIH HHS, United States
    Id: UL1 DE019585
  • Agency: NIGMS NIH HHS, United States
    Id: RL1-GM084437
  • Agency: NCI NIH HHS, United States
    Id: RL1-CA133834
  • Agency: NHGRI NIH HHS, United States
    Id: RL1 HG004671
  • Agency: NCI NIH HHS, United States
    Id: RL1 CA133834
  • Agency: NIGMS NIH HHS, United States
    Id: RL1 GM084437
  • Agency: NHGRI NIH HHS, United States
    Id: RL1-HG004671

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


BioMart Project (tool)

RRID:SCR_002987

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 4,2023.Platform provides free software and data services to international scientific community in order to foster scientific collaboration and facilitate scientific discovery process. Project adheres to open source philosophy that promotes collaboration and code reuse.

View all literature mentions

New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

View all literature mentions