title: Nuclear factor kappaB activation and antiapoptosis in mucosa-associated lymphoid tissue lymphoma.
abstract: Three distinct chromosomal translocations, t(11;18), t(1;14), and t(14;18), involving the API2-MALT1 fusion protein, BCL10, and MALT1 have been convincingly implicated in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas. Recent genetic and biochemical studies have indicated that BCL10 and MALT1 form a physical and functional complex and are both essential for nuclear factor kappaB (NF-kappaB) activation by antigen receptor stimulation in lymphocytes. API2-MALT1 can bypass the BCL10/MALT1 pathway linking to NF-kappaB activation, thereby inducing antigen receptor-independent events of lymphocytes. BCL10/MALT1- and API2-MALT1-induced NF-kappaB activation can be assumed to be able to contribute to antiapoptosis, probably through NF-kappaB-mediated up-regulation of several apoptotic inhibitor genes. We also have provided direct evidence that API2-MALT1 can exert an antiapoptotic effect, in part through its direct interaction with apoptotic regulators. We therefore hypothesize that the antiapoptotic effect of API2-MALT1 may be mediated by the interaction with apoptotic regulators as well as by the up-regulation of apoptotic inhibitor genes. Finally, we hope that further studies will stimulate research leading to the development of therapeutic drugs that specifically inhibit the antigen receptor-stimulated NF-kappaB activation pathway. Such drugs should be useful for interfering with inappropriate proliferation of lymphocytes associated with inflammatory and neoplastic disorders, including MALT lymphomas.
authors.affiliation: Aichi Cancer Center Research Institute, Nagoya, Japan. yhosokaw@aichi-cc.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
mesh_terms: D017209:Apoptosis; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D011946:Receptors, Antigen / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D011946:Receptors, Antigen