title: Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines.
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.
authors.affiliation: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hailfinger
authors.forename: Hendrik
authors.initials: H
authors.lastname: Nogai
authors.forename: Christiane
authors.initials: C
authors.lastname: Pelzer
authors.forename: Maike
authors.initials: M
authors.lastname: Jaworski
authors.forename: Katrin
authors.initials: K
authors.lastname: Cabalzar
authors.forename: Jean-Enno
authors.initials: JE
authors.lastname: Charton
authors.forename: Montserrat
authors.initials: M
authors.lastname: Guzzardi
authors.forename: Chantal
authors.initials: C
authors.lastname: Décaillet
authors.forename: Michael
authors.initials: M
authors.lastname: Grau
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Peter
authors.initials: P
authors.lastname: Lenz
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: Margot
authors.initials: M
authors.lastname: Thome
mesh_terms: D020169:Caspases / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; C498143:RELA protein, human; C497593:RELB protein, human; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein