Activation of NF-kappa B and inhibition of p53-mediated apoptosis by API2/mucosa-associated lymphoid tissue 1 fusions promote oncogenesis

作者：Stoffel A^*; Chaurushiya M; Singh B; Levine AJ

来源：Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(24): 9079-9084.

DOI：10.1073/pnas.0402415101

Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by the t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding structurally distinct API2/MALT1 fusion proteins. In this study, we provide functional evidence for the contribution of API2/MALT1 fusion proteins to transformation of cells in culture by activating the NF-kappaB pathway through a ReIB/p50 dimer. Using microchip gene expression analysis, we demonstrate that different forms of the API2/MALT1 proteins activate both unique and overlapping gene programs in cells. in addition to this genome reprogramming, expression of distinct API2/MALT1 fusion products inhibits DNA damage-induced, p53-mediated apoptosis in an NF-kappaB-dependent manner. Collectively, these data reveal previously unknown functional diversity among API2/MALT1 fusion products and their function in NF-kappaB signaling as it connects to the apoptotic program, a pathway with strong relevance to cancer. Furthermore, they provide evidence underlying the emerging role of the NF-kappaB signaling pathway in the inhibition of apoptosis.

• 出版日期2004-6-15