CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MIB2: a novel BCL10-interacting protein
Autor/es:
STEMPIN, CC; CHI, L; HAECKER, H AND REDECKE V.
Lugar:
Buenos Aires
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
Activation through the T-cell receptor (TCR) leads to the initiation of multiple signaling cascades that regulate survival, cytokine production and proliferation of T-cells. A key event upon TCR engagement is the formation of a signaling complex between CARMA1, BCL10 and MALT1, referred to as CBM complex. These three molecules interact physically and functionally. The components of this complex were found to be essential for Tcell activation, in particular by controlling the NF-kB and MAP kinase signal transduction pathways. Even though the role of the CBM complex in T-cell activation is well established, little is known about the signaling events between the CBM complex and downstream effector molecules. Using an affinity purification/mass spectrometry approach we have identified Mind Bomb-2 (MIB2) as a novel BCL10-interacting protein. MIB2 is constitutively associated with BCL10 at low levels and significantly recruited upon activation. Overexpression of MIB2 leads to a strong increase in transcriptional NF-kB activity, indicating that MIB2 may represent a critical factor for BCL10-dependent NF-kB activation. We have characterized the molecular mechanism of MIB2-dependent NF-kB activation and identified the structural domains of MIB2 that control BCL10 interaction and NF-kB activation. Identification of molecular events downstream the CBM complex will further improve our understanding of T-cell activation, a critical event not only in the defense against pathogens, but also in the initiation and progression of inflammatory diseases such as allergy and asthma or autoimmunity.