| Abstract: |
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-κB pathway through a RelB/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-κB-dependent manner. Collectively, these data reveal previously unknown functional diversity among API2/MALT1 fusion products and their function in NF-κB 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-κB signaling pathway in the inhibition of apoptosis. |
| Keywords: |
signal transduction; controlled study; unclassified drug; oncoprotein; genetics; proto-oncogene proteins; nonhuman; protein function; ultraviolet radiation; animal cell; mouse; animal; metabolism; animals; mice; dna damage; apoptosis; gene expression; nuclear protein; cell line; inflammation; transcription factor; immunoglobulin enhancer binding protein; genetic transcription; transcription, genetic; pathology; transfection; protein p53; radiation exposure; physiology; carcinogenesis; animalia; transcription factors; cell transformation, neoplastic; nuclear proteins; gene activation; chemistry; drug antagonism; hybrid protein; genetic transfection; cell culture; cell transformation; inhibitor of apoptosis protein; nf-kappa b; tumor suppressor proteins; recombinant proteins; recombinant protein; oncogene proteins, fusion; tumor suppressor protein p53; dimerization; dna microarray; ultraviolet rays; tumor suppressor protein; cell strain 3t3; nih 3t3 cells; chimeric protein; dimer; chromosome translocation 11; mucosa associated lymphoid tissue lymphoma; protein p50; transcription factor relb; lymphoma, mucosa-associated lymphoid tissue; humans; human; priority journal; article; api2 mucosa associated lymphoid tissue 1 fusion protein; api2 protein; mucosa associated lymphoid tissue 1 protein; api2 malt1 fusion protein, human; api2-malt1 fusion protein, human; relb protein, human; relb protein, mouse
|
