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JCS ePress online publication date 18 Mar 2008
doi: 10.1242/jcs.021105

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Research Article

A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-{kappa}B


Romania Stilo, Ettore Varricchio, Domenico Liguoro, Antonio Leonardi, and Pasquale Vito*
* Author for correspondence (e-mail: vito{at}unisannio.it)

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 {kappa}B (NF-{kappa}B) 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 IKK{gamma}/NEMO, thereby suppressing activation of NF-{kappa}B. Together, our results further define the molecular mechanisms that control activation of NF-{kappa}B and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells.






© The Company of Biologists Ltd 2008