Molecular Pathogenesis of MALT Lymphoma

Figure 1

Translocations affecting the NF-κB activation pathway. (a) Signaling from the TLR, IL-1R, and antigen receptor activates the canonical NF-κB pathway, which is characterized by activation of the IKK complex, phosphorylation, and degradation of IκB. TNFAIP3 is a negative regulator. (b) t(1;14)(p22;q32) results in the nuclear overexpression of the BCL10 protein. It is believed to form oligomers through its CARD domain and so it triggers MALT1 oligomerization and aberrant NF-κB activation. (c) t(14;18)(q32;q21) causes overexpression of MALT1. It is thought that it oligomerizes through interaction with BCL10 causing NF-κB activation. (d) t(11;18)(q21;q21), the BIR domain of the BIRC2-MALT1, mediates self-oligomerization leading to an activation of NF-κB. TLR: Toll-like receptor; IL-1R: interleukin-1 receptor; BCR: B cell receptor; TCR: T cell receptor; RIP1: receptor interacting protein 1; TRAF: TNF-associated factor; TAK1: transforming growth factor beta activated kinase 1; TAB: TAK binding protein; IKK: inhibitor of NF-κB kinase; IκB: inhibitor of NF-κB.

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