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

Cell Cycle. 2004 Aug;3(8):1017-20. Epub 2004 Aug 25.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Humans
  • NF-kappa B / metabolism*
  • Oncogene Proteins, Fusion / metabolism*
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / metabolism*
  • fas Receptor / metabolism*

Substances

  • API2-MALT1 fusion protein, human
  • NF-kappa B
  • Oncogene Proteins, Fusion
  • Tumor Suppressor Protein p53
  • fas Receptor