Activation of NF-κB and inhibition of p53-mediated apoptosis by API2/mucosa-associated lymphoid tissue 1 fusions promote oncogenesis Academic Article uri icon


MeSH Major

  • Cell Transformation, Neoplastic
  • Lymphoma, B-Cell, Marginal Zone
  • NF-kappa B
  • Oncogene Proteins, Fusion
  • Tumor Suppressor Protein p53


  • 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 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-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.

publication date

  • June 15, 2004



  • Academic Article



  • eng

PubMed Central ID

  • PMC428476

Digital Object Identifier (DOI)

  • 10.1073/pnas.0402415101

PubMed ID

  • 15184680

Additional Document Info

start page

  • 9079

end page

  • 84


  • 101


  • 24