Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines.
- Hailfinger S Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
- Nogai H
- Pelzer C
- Jaworski M
- Cabalzar K
- Charton JE
- Guzzardi M
- Décaillet C
- Grau M
- Dörken B
- Lenz P
- Lenz G
- Thome M
- 2011-08-30
Published in:
- Proceedings of the National Academy of Sciences of the United States of America. - 2011
Caspases
Cell Line, Tumor
Humans
Lymphocyte Activation
Lymphocytes
Lymphoma, Large B-Cell, Diffuse
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
NF-kappa B
Neoplasm Proteins
Transcription Factor RelA
Transcription Factor RelB
English
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1073/pnas.1105020108
- PMID 21873235
- Persistent URL
- https://sonar.ch/global/documents/43015
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