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 RIS Download
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