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 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.
Stilo
Romania
R
Dip. Scienze Biologiche ed Ambientali, Università degli Studi del Sannio di Benevento, Via Port'Arsa 11, 82100 Benevento, Italy.
Varricchio
Ettore
E
Liguoro
Domenico
D
Leonardi
Antonio
A
Vito
Pasquale
P
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3