The molecular complex containing BCL10 and CARMA [CARD (caspase recruitment domain)-containing MAGUK (membrane-associated guanylate kinase)] proteins has recently been identified as a key component in the signal transduction pathways that regulate activation of the transcription factor NF-κB (nuclear factor κB) in lymphoid and non-lymphoid cells. Assembly of complexes containing BCL10 and CARMA proteins relies on homophilic interactions established between the CARDs of these proteins. In order to identify BCL10-inhibitory peptides, we have established a method of assaying peptides derived from the CARD of BCL10 in binding competition assays of CARD–CARD self-association. By this procedure, a short peptide corresponding to amino acid residues 91–98 of BCL10 has been selected as an effective inhibitor of protein self-association. When tested in cell assays for its capacity to block NF-κB activation, this peptide represses activation of NF-κB mediated by BCL10, CARMA3 and PMA/ionomycin stimulation. Collectively, these results indicate that residues 91–98 of BCL10 are involved in BCL10 self-association and also participate in the interaction with external partners. We also show that blocking of the CARD of BCL10 may potentially be used for the treatment of pathological conditions associated with inappropriate NF-κB activation.
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Research Article|
August 27 2009
Generation and functional characterization of a BCL10-inhibitory peptide that represses NF-κB activation
Daniela Marasco;
Daniela Marasco
*Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy
†Dipartimento di Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone, 16, 80134 Napoli, Italy
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Romania Stilo;
Romania Stilo
‡Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy
§BioGeM Consortium, Via Camporeale, 83031 Ariano Irpino, Italy
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Annamaria Sandomenico;
Annamaria Sandomenico
*Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy
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Simona Maria Monti;
Simona Maria Monti
*Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy
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Barbara Tizzano;
Barbara Tizzano
*Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy
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Antonia de Capua;
Antonia de Capua
*Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy
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Ettore Varricchio;
Ettore Varricchio
‡Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy
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Domenico Liguoro;
Domenico Liguoro
∥Centro di Endocrinologia ed Oncologia Sperimentale, 80131 Napoli, Italy
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Tiziana Zotti;
Tiziana Zotti
‡Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy
§BioGeM Consortium, Via Camporeale, 83031 Ariano Irpino, Italy
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Silvestro Formisano;
Silvestro Formisano
¶Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Via Pansini 5, 80131, Napoli, Italy
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Menotti Ruvo;
Menotti Ruvo
1
*Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy
1Correspondence may be addressed to either of these authors (email menotti.ruvo@unina.it or vito@unisannio.it).
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Pasquale Vito
Pasquale Vito
1
‡Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy
§BioGeM Consortium, Via Camporeale, 83031 Ariano Irpino, Italy
1Correspondence may be addressed to either of these authors (email menotti.ruvo@unina.it or vito@unisannio.it).
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Publisher: Portland Press Ltd
Received:
January 09 2009
Revision Received:
June 16 2009
Accepted:
June 18 2009
Accepted Manuscript online:
June 18 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 422 (3): 553–561.
Article history
Received:
January 09 2009
Revision Received:
June 16 2009
Accepted:
June 18 2009
Accepted Manuscript online:
June 18 2009
Citation
Daniela Marasco, Romania Stilo, Annamaria Sandomenico, Simona Maria Monti, Barbara Tizzano, Antonia de Capua, Ettore Varricchio, Domenico Liguoro, Tiziana Zotti, Silvestro Formisano, Menotti Ruvo, Pasquale Vito; Generation and functional characterization of a BCL10-inhibitory peptide that represses NF-κB activation. Biochem J 15 September 2009; 422 (3): 553–561. doi: https://doi.org/10.1042/BJ20090055
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