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Deregulation of the antigen-induced NF-κB signaling pathway in the development of human B-cells lymphomas

Abstract : The adaptive immune response is initiated when microbial or tumor-specific molecules are recognized by antigen receptors present at lymphocyte cell surface. Engagement of these immunoreceptors induces signaling cascades that ultimately activate the transcription factors NF-κB (Nuclear Factor-κB) and NFAT (nuclear factor of activated T-cells) responsible for the establishment of gene expression programs controlling the stimulation, proliferation and survival of activated lymphocytes. Cloning the products of three distinct translocation events found in lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) led to the identification and characterization of a novel NF-κB-activating complex following antigenic stimulation composed by the CARMA1, BCL10, and MALT1 proteins and called the CBM complex. Since the identification of this complex, other regulatory components were discovered which greatly improve our understanding of this signaling pathways. Interestingly, CBM complex activity is not only altered in MALT lymphomas but also in a subtype activated B cell-like (ABC) of diffuse large B-cell (DLBCL) lymphoma. In this review, we described the key players involved in antigen-induced NF-κB activation and cover the recent advances in the molecular mechanisms that are responsible for the regulation of the components of the CBM complex. Understanding these mechanisms is critical for the elucidation of the role of this NF-κB signaling network in both normal and pathologic conditions and we described how deregulation of this network leads to the uncontrolled activation of NF-κB and development of two particular subtypes of human B cell lymphomas: the MALT and the DLBCL lymphomas.
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Submitted on : Thursday, March 6, 2014 - 12:15:33 PM
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Nassima Messali, Pierre Génin, Robert Weil. Deregulation of the antigen-induced NF-κB signaling pathway in the development of human B-cells lymphomas. Journal of Leukemia, 2013, 1 (1), pp.1-11. ⟨10.4172/2329-6917.1000105⟩. ⟨pasteur-00956355⟩



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