• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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