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Signal-responsiveness of Ikappa B kinases is determined by Cdc37-assisted transient interaction with Hsp90

Item Type:Article
Title:Signal-responsiveness of Ikappa B kinases is determined by Cdc37-assisted transient interaction with Hsp90
Creators Name:Hinz, M. and Broemer, M. and Coel Arslan, S. and Otto, A. and Mueller, E.C. and Dettmer, R. and Scheidereit, C.
Abstract:The IkappaB kinase (IKK) holocomplex, containing the kinases IKKalpha, IKKbeta and the scaffold NEMO (NF-kappaB essential modifier), mediates activation of NF-kappaB by numerous physiological stimuli. Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal transduction are indistinct. Using an RNAi approach, we demonstrate that Cdc37 recruits Hsp90 to the IKK complex in a transitory manner, preferentially via IKKalpha. Binding is conferred by N-terminal as well as C-terminal residues of Cdc37. Cdc37 is essential for the maturation of de novo synthesized IKKs into enzymatically competent kinases, but not for assembly of an IKK holocomplex. Mature IKKs, T-loop phosphorylated after stimulation either by receptor-mediated signaling or upon DNA damage, further require Hsp90-Cdc37 to generate an activated state. Thus, the present data denote Hsp90-Cdc37 as a transiently acting essential regulatory component of IKK signaling.
Keywords:Cell Cycle Proteins, Cell Line, Chaperonins, HeLa Cells, HSP90 Heat-Shock Proteins, I-kappa B Kinase, Signal Transduction, Tacrolimus Binding Proteins
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:282
Number:44
Page Range:32311-32319
Date:2 November 2007
Additional Information:Copyright (c) 2007 by The American Society for Biochemistry and Molecular Biology
Official Publication:https://doi.org/10.1074/jbc.M705785200
PubMed:View item in PubMed

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