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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.

Pubmed ID: 11864612


  • Chen G
  • Cao P
  • Goeddel DV


Molecular cell

Publication Data

February 26, 2002

Associated Grants


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