Actvation of NF-kappaB by the API2/MALT1 fusions inhibits p53 dependant but not FAS induced apoptosis: a directional link between NF-kappaB and p53.
Interactions between survival pathways and apoptotic cascades play a determinant role in the maintenance of neoplastic clone proliferation and impaired response to apoptosis. Recently, we established a novel interplay between the NF-kappaB survival- and p53 death-pathways in a tumor model system that represents the most common extranodal lymphoid cell neoplasia, MALT (Mucosa Associated Lymphoid Tissue) lymphoma. MALTs are genetically characterized by the t(11;18)(q21;q21) chromosomal translocation that results in API2/MALT1 fusion products. It was shown that distinct API2/MALT1 chimeric proteins function as oncogenes that bilaterally confer a proliferative advantage to the neoplastic clone by activating the NF-kappaB signaling pathway and also inhibiting p53 mediated cell death. Here, we demonstrate that API2/MALT1 mediated inhibition of apoptosis is p53 specific, as distinct API2/MALT1 fusion proteins fail to protect cells from FAS induced cell death. Furthermore, we demonstrate that API2/MALT1 mediated NF-kappaB activation does not alter p53 protein levels or subcellular localization suggesting a post-translational or indirect mechanism of p53 deregulation.
The Rockefeller University, Laboratory for Cancer Biology, New York, New York 10021, USA. stoffea@rockefeller.edu
Archontoula
A
Stoffel
Arnold J
AJ
Levine
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
C415943:API2-MALT1 fusion protein, human; D016328:NF-kappa B; D015514:Oncogene Proteins, Fusion; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor