University of Sussex
Browse
mmc2.pdf (13.01 MB)

Differential regulation of G1 CDK complexes by the Hsp90-Cdc37 chaperone system

Download (13.01 MB)
journal contribution
posted on 2023-06-09, 08:38 authored by Stephen T Hallett, Martyna W Pastok, R Marc L Morgan, Anita Wittner, Katie L I M Blundell, Ildiko Felletar, Stephen R Wedge, Chrisostomos ProdromouChrisostomos Prodromou, Martin E M Noble, Laurence PearlLaurence Pearl, Jane A Endicott
Selective recruitment of protein kinases to the Hsp90 system is mediated by the adaptor co-chaperone Cdc37. We show that assembly of CDK4 and CDK6 into protein complexes is differentially regulated by the Cdc37-Hsp90 system. Like other Hsp90 kinase clients, binding of CDK4/6 to Cdc37 is blocked by ATP-competitive inhibitors. Cdc37-Hsp90 relinquishes CDK6 to D3- and virus-type cyclins and to INK family CDK inhibitors, whereas CDK4 is relinquished to INKs but less readily to cyclins. p21CIP1 and p27KIP1 CDK inhibitors are less potent than the INKs at displacing CDK4 and CDK6 from Cdc37. However, they cooperate with the D-type cyclins to generate CDK4/6-containing ternary complexes that are resistant to cyclin D displacement by Cdc37, suggesting a molecular mechanism to explain the assembly factor activity ascribed to CIP/KIP family members. Overall, our data reveal multiple mechanisms whereby the Hsp90 system may control formation of CDK4- and CDK6-cyclin complexes under different cellular conditions.

Funding

‘Mechanisms of client protein activation and regulation by the Hsp90 molecular chaperone system; Wellcome Trust; 095605/Z/11/Z

History

Publication status

  • Published

File Version

  • Published version

Journal

Cell Reports

ISSN

2211-1247

Publisher

Elsevier

Issue

5

Volume

21

Page range

1386-1398

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-11-06

First Open Access (FOA) Date

2017-11-06

First Compliant Deposit (FCD) Date

2017-11-06

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC