Bcl10 and MALT1, Independent Targets of Chromosomal Translocation in MALT Lymphoma, Cooperate in a Novel NF-κB Signaling Pathway

Peter C. Lucas, Masakatsu Yonezumi, Naohiro Inohara, Linda M. McAllister-Lucas, Mohamed E. Abazeed, Felicia F. Chen, Shoji Yamaoka, Masao Seto, Gabriel Núñez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

382 Scopus citations

Abstract

At least two distinct recurrent chromosomal translocations have been implicated in the pathogenesis of MALT lymphoma. The first, t(1;14), results in the transfer of the entire Bcl10 gene to chromosome 14 wherein Bcl10 expression is inappropriately stimulated by the neighboring Ig enhancer. The second, t(11;18), results in the synthesis of a novel fusion protein, API2-MALT1. Until now, no common mechanism of action has been proposed to explain how the products of these seemingly unrelated translocations may contribute to the same malignant process. We show here that Bcl10 and MALT1 form a strong and specific complex within the cell, and that these proteins synergize in the activation of NF-κB. The data support a mechanism of action whereby Bcl10 mediates the oligomerization and activation of the MALT1 caspase-like domain. This subsequently activates the IKK complex through an unknown mechanism, setting in motion a cascade of events leading to NF-κB induction. Furthermore, the API2-MALT1 fusion protein also strongly activates NF-κB and shows dependence upon the same downstream signaling factors. We propose a model whereby both the Bcl10-MALT1 complex and the API2-MALT1 fusion protein activate a common downstream signaling pathway that originates with the oligomerization-dependent activation of the MALT1 caspase-like domain.

Original languageEnglish (US)
Pages (from-to)19012-19019
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number22
DOIs
StatePublished - Jun 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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