NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-κB activation
- Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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Communicated by Arthur Weiss, University of California, San Francisco, CA, January 2, 2008 (received for review September 19, 2007)
Abstract
The mechanism by which the Carma1–Bcl10–MALT1 (CBM) complex couples T cell antigen receptor (TCR) signaling to IκB kinase (IKK) and NF-κB 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-κB activation. Therefore, the regulated ubiquitination of Bcl10 and its recognition by NEMO are a critical link between the CBM complex, IKK recruitment, and NF-κB activation.
Footnotes
- *To whom correspondence should be addressed. E-mail: jda{at}pop.nci.nih.gov
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Author contributions: C.-J.W. and J.D.A. designed research; C.-J.W. performed research; C.-J.W. and J.D.A. analyzed data; and C.-J.W. and J.D.A. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0712313105/DC1.
