Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines.
Data(s) |
2011
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Resumo |
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. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_4C1E52575884 isbn:1091-6490 (Electronic) pmid:21873235 doi:10.1073/pnas.1105020108 isiid:000294425900048 |
Idioma(s) |
en |
Fonte |
Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 35, pp. 14596-14601 |
Palavras-Chave | #Caspases/physiology; Cell Line, Tumor; Humans; Lymphocyte Activation; Lymphocytes/metabolism; Lymphoma, Large B-Cell, Diffuse/etiology; Lymphoma, Large B-Cell, Diffuse/metabolism; NF-kappa B/metabolism; Neoplasm Proteins/physiology; Transcription Factor RelA/metabolism; Transcription Factor RelB/metabolism |
Tipo |
info:eu-repo/semantics/article article |