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Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14596-601. doi: 10.1073/pnas.1105020108. Epub 2011 Aug 22.

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

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  • 1Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.

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.

PMID:
21873235
[PubMed - indexed for MEDLINE]
PMCID:
PMC3167514
Free PMC Article

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