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Malt1-dependent RelB cleavage promotes canonical NF-κB activation in lymphocytes and lymphoma cell lines

Item Type:Article
Title:Malt1-dependent RelB cleavage promotes canonical NF-κB activation in lymphocytes and lymphoma cell lines
Creators Name:Hailfinger, S. and Nogai, H. and Pelzer, C. and Jaworski, M. and Cabalzar, K. and Charton, J.E. and Guzzardi, M. and Decaillet, C. and Grau, M. and Doerken, B. and Lenz, P. and Lenz, G. and Thome, M.
Abstract:The protease activity of the paracaspase Malt1 contributes to antigen receptor-mediated lymphocyte activation and lymphomagenesis. Malt1 activity is required for optimal NF-{kappa}B activation, but little is known about the responsible substrate(s). Here we report that Malt1 cleaved the NF-{kappa}B family member RelB after Arg-85. RelB cleavage induced its proteasomal degradation and specifically controlled DNA binding of RelA- or c-Rel-containing NF-{kappa}B complexes. Overexpression of RelB inhibited expression of canonical NF-{kappa}B target genes and led to impaired survival of diffuse large B-cell lymphoma cell lines characterized by constitutive Malt1 activity. These findings identify a central role for Malt1-dependent RelB cleavage in canonical NF-{kappa}B activation and thereby provide a rationale for the targeting of Malt1 in immunomodulation and cancer treatment.
Keywords:Signal Transduction, T-Cell Receptor
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences (U.S.A.)
Page Range:14596-14601
Date:30 August 2011
Official Publication:https://doi.org/10.1073/pnas.1105020108
PubMed:View item in PubMed

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