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IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex.

Pro-inflammatory cytokines activate the transcription factor NF-kappaB by stimulating the activity of a protein kinase that phosphorylates IkappaB, an inhibitor of NF-kappaB, at sites that trigger its ubiquitination and degradation. This results in the nuclear translocation of freed NF-kappaB dimers and the activation of transcription of target genes. Many of these target genes code for immunoregulatory proteins. A large, cytokine-responsive IkappaB kinase (IKK) complex has been purified and the genes encoding two of its subunits have been cloned. These subunits, IKK-alpha and IKK-beta, are protein kinases whose function is needed for NF-kappaB activation by pro-inflammatory stimuli. Here, by using a monoclonal antibody against IKK-alpha, we purify the IKK complex to homogeneity from human cell lines. We find that IKK is composed of similar amounts of IKK-alpha, IKK-beta and two other polypeptides, for which we obtained partial sequences. These polypeptides are differentially processed forms of a third subunit, IKK-gamma. Molecular cloning and sequencing indicate that IKK-gamma is composed of several potential coiled-coil motifs. IKK-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex. An IKK-gamma carboxy-terminal truncation mutant that still binds IKK-beta blocks the activation of IKK and NF-kappaB.

Pubmed ID: 9751060

Authors

  • Rothwarf DM
  • Zandi E
  • Natoli G
  • Karin M

Journal

Nature

Publication Data

September 17, 1998

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Catalysis
  • Cloning, Molecular
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • I-kappa B Kinase
  • Jurkat Cells
  • Leucine Zippers
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Secondary
  • Protein-Serine-Threonine Kinases
  • Sequence Deletion