A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB

The molecular complex containing CARMA proteins, BCL10 and TRAF6 has been identified recently as a key component in the signal transduction pathways that regulate activation of the nuclear factor kappaB (NF-kappaB) transcription factor. Here, we report that the inducible protein A20 negatively regul...

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Published inJournal of cell science Vol. 121; no. Pt 8; pp. 1165 - 1171
Main Authors Stilo, Romania, Varricchio, Ettore, Liguoro, Domenico, Leonardi, Antonio, Vito, Pasquale
Format Journal Article
LanguageEnglish
Published England 15.04.2008
Subjects
Adaptor Proteins, Signal Transducing - physiology
B-Cell CLL-Lymphoma 10 Protein
CARD Signaling Adaptor Proteins - physiology
Cell Line
DNA-Binding Proteins
Humans
Intracellular Signaling Peptides and Proteins - physiology
NF-kappa B - metabolism
Nuclear Proteins - physiology
Tumor Necrosis Factor alpha-Induced Protein 3
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Summary:The molecular complex containing CARMA proteins, BCL10 and TRAF6 has been identified recently as a key component in the signal transduction pathways that regulate activation of the nuclear factor kappaB (NF-kappaB) transcription factor. Here, we report that the inducible protein A20 negatively regulates these signaling cascades by means of its deubiquitylation activity. We show that A20 perturbs assembly of the complex containing CARMA3, BCL10 and IKKgamma/NEMO, thereby suppressing activation of NF-kappaB. Together, our results further define the molecular mechanisms that control activation of NF-kappaB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells.
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ISSN:0021-9533
DOI:10.1242/jcs.021105