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

Hailfinger, S.; Nogai, H.; Pelzer, C.; Jaworski, M.; Cabalzar, K.; Charton, J.E.; Guzzardi, M.; Decaillet, C.; Grau, M.; Doerken, B.; Lenz, P.; Lenz, G.; Thome, M.

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

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Item Type:	Article
Title:	Malt1-dependent RelB cleavage promotes canonical NF-κB activation in lymphocytes and lymphoma cell lines
Creators Name:	Hailfinger, S., Nogai, H., Pelzer, C., Jaworski, M., Cabalzar, K., Charton, J.E., Guzzardi, M., Decaillet, C., Grau, M., Doerken, B., Lenz, P., 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
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Volume:	108
Number:	35
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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