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ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB.

Nuclear factor kappaB (NF-kappaB) plays a pivotal role in inflammation, immunity, stress responses, and protection from apoptosis. Canonical activation of NF-kappaB is dependent on the phosphorylation of the inhibitory subunit IkappaBalpha that is mediated by a multimeric, high molecular weight complex, called IkappaB kinase (IKK) complex. This is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, NEMO/IKKgamma. The latter protein is essential for the activation of IKKs and NF-kappaB, but its mechanism of action is not well understood. Here we identified ABIN-1 (A20 binding inhibitor of NF-kappaB) as a NEMO/IKKgamma-interacting protein. ABIN-1 has been previously identified as an A20-binding protein and it has been proposed to mediate the NF-kappaB inhibiting effects of A20. We find that both ABIN-1 and A20 inhibit NF-kappaB at the level of the IKK complex and that A20 inhibits activation of NF-kappaB by de-ubiquitination of NEMO/IKKgamma. Importantly, small interfering RNA targeting ABIN-1 abrogates A20-dependent de-ubiquitination of NEMO/IKKgamma and RNA interference of A20 impairs the ability of ABIN-1 to inhibit NF-kappaB activation. Altogether our data indicate that ABIN-1 physically links A20 to NEMO/IKKgamma and facilitates A20-mediated de-ubiquitination of NEMO/IKKgamma, thus resulting in inhibition of NF-kappaB.

Pubmed ID: 16684768


  • Mauro C
  • Pacifico F
  • Lavorgna A
  • Mellone S
  • Iannetti A
  • Acquaviva R
  • Formisano S
  • Vito P
  • Leonardi A


The Journal of biological chemistry

Publication Data

July 7, 2006

Associated Grants


Mesh Terms

  • Animals
  • Binding Sites
  • Catalytic Domain
  • Cell Line
  • Cysteine Endopeptidases
  • DNA-Binding Proteins
  • Humans
  • I-kappa B Kinase
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mutation
  • NF-kappa B
  • Nuclear Proteins
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Proteins
  • Rabbits
  • Ubiquitin