Biochem J. 2009 Aug 27;422(3):553-61.

Generation and functional characterization of a BCL10-inhibitory peptide that represses NF-kappaB activation.External

Marasco, D., Stilo, R., Sandomenico, A., Monti, S. M., Tizzano, B., de Capua, A., Varricchio, E., Liguoro, D., Zotti, T., Formisano, S., Ruvo, M., Vito, P.,
--- - Istituto di Biostrutture e Bioimmagini (IBB), CNR, 80134, Napoli, Italy.
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-kappaB (nuclear factor kappaB) 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-kappaB activation, this peptide represses activation of NF-kappaB 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-kappaB activation.
PMID: 19538180External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Bcl-10 Link Bcl-10 Co-immunoprecipitation HEK293 Not specified 1-127 Not specified 1-127 19538180
CARD Bcl-10 Link CARD10 Co-immunoprecipitation HEK293 Not specified 1-127 Not specified Not specified 19538180
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
CARD Bcl-10 Link Bcl-10 Fluorescence probe labeling 3.0μM 19538180
(Link: click this icon to show interactions only between the two corresponding DDs)