TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90.

The IKK complex, containing two catalytic subunits IKKalpha and IKKbeta and a regulatory subunit NEMO, plays central roles in signal-dependent activation of NF-kappaB. We identify Cdc37 and Hsp90 as two additional components of the IKK complex. IKKalpha/IKKbeta/NEMO and Cdc37/Hsp90 form an approximately 900 kDa heterocomplex, which is assembled via direct ...
interactions of Cdc37 with Hsp90 and with the kinase domain of IKKalpha/IKKbeta. Geldanamycin (GA), an antitumor agent that disrupts the formation of this heterocomplex, prevents TNF-induced activation of IKK and NF-kappaB. GA treatment reduces the size of the IKK complex and abolishes TNF-dependent recruitment of the IKK complex to TNF receptor 1 (TNF-R1). Therefore, heterocomplex formation with Cdc37/Hsp90 is a prerequisite for TNF-induced activation and trafficking of IKK from the cytoplasm to the membrane.
Mesh Terms:
Antigens, CD, Benzoquinones, Carrier Proteins, Cell Cycle Proteins, Chaperonins, Drosophila Proteins, Enzyme Activation, HSP90 Heat-Shock Proteins, Hela Cells, Humans, I-kappa B Kinase, Interleukin-1, Lactams, Macrocyclic, Mitogen-Activated Protein Kinases, Molecular Chaperones, Multienzyme Complexes, NF-kappa B, Protein Interaction Mapping, Protein Structure, Tertiary, Protein Transport, Protein-Serine-Threonine Kinases, Quinones, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Transcription, Genetic, Tumor Necrosis Factor-alpha
Mol. Cell
Date: Feb. 01, 2002
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