[HTML][HTML] TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90
G Chen, P Cao, DV Goeddel - Molecular cell, 2002 - cell.com
G Chen, P Cao, DV Goeddel
Molecular cell, 2002•cell.comThe IKK complex, containing two catalytic subunits IKKα and IKKβ and a regulatory subunit
NEMO, plays central roles in signal-dependent activation of NF-κB. We identify Cdc37 and
Hsp90 as two additional components of the IKK complex. IKKα/IKKβ/NEMO and
Cdc37/Hsp90 form an∼ 900 kDa heterocomplex, which is assembled via direct interactions
of Cdc37 with Hsp90 and with the kinase domain of IKKα/IKKβ. Geldanamycin (GA), an
antitumor agent that disrupts the formation of this heterocomplex, prevents TNF-induced …
NEMO, plays central roles in signal-dependent activation of NF-κB. We identify Cdc37 and
Hsp90 as two additional components of the IKK complex. IKKα/IKKβ/NEMO and
Cdc37/Hsp90 form an∼ 900 kDa heterocomplex, which is assembled via direct interactions
of Cdc37 with Hsp90 and with the kinase domain of IKKα/IKKβ. Geldanamycin (GA), an
antitumor agent that disrupts the formation of this heterocomplex, prevents TNF-induced …
Abstract
The IKK complex, containing two catalytic subunits IKKα and IKKβ and a regulatory subunit NEMO, plays central roles in signal-dependent activation of NF-κB. We identify Cdc37 and Hsp90 as two additional components of the IKK complex. IKKα/IKKβ/NEMO and Cdc37/Hsp90 form an ∼900 kDa heterocomplex, which is assembled via direct interactions of Cdc37 with Hsp90 and with the kinase domain of IKKα/IKKβ. Geldanamycin (GA), an antitumor agent that disrupts the formation of this heterocomplex, prevents TNF-induced activation of IKK and NF-κB. 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.
cell.com
