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NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation.

The mechanism by which the Carma1-Bcl10-MALT1 (CBM) complex couples T cell antigen receptor (TCR) signaling to IkappaB kinase (IKK) and NF-kappaB activation is not known. Here, we show that Bcl10 undergoes K63-linked polyubiquitination in response to T cell activation and subsequently binds NEMO, the regulatory subunit of IKK. This interaction requires the ubiquitin-binding activity of NEMO. The sites of Bcl10 ubiquitination were mapped to K31 and K63. Mutation of these residues did not affect TCR signaling-induced CBM complex assembly but prevented Bcl10 ubiquitination, NEMO binding, and NF-kappaB activation. Therefore, the regulated ubiquitination of Bcl10 and its recognition by NEMO are a critical link between the CBM complex, IKK recruitment, and NF-kappaB activation.

Pubmed ID: 18287044


  • Wu CJ
  • Ashwell JD


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

February 26, 2008

Associated Grants

  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Binding Sites
  • Escherichia coli
  • Humans
  • I-kappa B Kinase
  • Immunoblotting
  • Immunoprecipitation
  • Jurkat Cells
  • Luciferases
  • Mutation
  • NF-kappa B p50 Subunit
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • Ubiquitination