Malt1-dependent RelB Cleavage Promotes Canonical NF-kappaB Activation in Lymphocytes and Lymphoma Cell Lines

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Aug 30

PMID 21873235

Citations 104

Authors

Stephan Hailfinger

Hendrik Nogai

Christiane Pelzer

Maike Jaworski

Katrin Cabalzar

Jean-Enno Charton

Montserrat Guzzardi

Chantal Decaillet

Michael Grau

Bernd Dorken

Peter Lenz

Georg Lenz

Margot Thome

Affiliations

Soon will be listed here.

Abstract

The protease activity of the paracaspase Malt1 contributes to antigen receptor-mediated lymphocyte activation and lymphomagenesis. Malt1 activity is required for optimal NF-κB activation, but little is known about the responsible substrate(s). Here we report that Malt1 cleaved the NF-κB family member RelB after Arg-85. RelB cleavage induced its proteasomal degradation and specifically controlled DNA binding of RelA- or c-Rel-containing NF-κB complexes. Overexpression of RelB inhibited expression of canonical NF-κB 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-κB activation and thereby provide a rationale for the targeting of Malt1 in immunomodulation and cancer treatment.

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