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Autocleavage of the paracaspase MALT1 at Arg-781 attenuates NF-κB signaling and regulates the growth of activated B-cell like diffuse large B-cell lymphoma cells.
- Source :
-
PloS one [PLoS One] 2018 Jun 28; Vol. 13 (6), pp. e0199779. Date of Electronic Publication: 2018 Jun 28 (Print Publication: 2018). - Publication Year :
- 2018
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Abstract
- MALT1 controls several receptors-mediated signaling to nuclear factor κB (NF-κB) through both its scaffold and protease function. MALT1 protease activity is shown to inactivate several negative regulators of NF-κB signaling and augment NF-κB activation ability. In this study, MALT1 was demonstrated to autoprocess itself in the presence of oligomerization-competent BCL10. Cleavage occurred after Arginine 781 located in the C-terminus of MALT1. Shortened MALT1 cleavage products showed attenuated binding ability with TRAF6. Its NF-κB activation ability was also weakened. Various MALT1 constructs including wild type, catalytically-inactive (MALT1&#95;C464A), cleavage-defective (MALT1&#95;R781L), or truncated (MALT1&#95;1-781) form of MALT1 was introduced into MALT1-knocked-down-Jurkat T cells. Cleavage-defective MALT1&#95;R781L retained its proteolytic and initial IκBα phosphorylation activity as MALT1. Truncated MALT1&#95;1-781 mutant showed weakness in IκBα phosphorylation and the expression of NF-κB targets IL-2 and IFN-γ. Cleavage at R781 was detectable but marginal after activation with TPA/ionomycin or anti-CD3 antibody in lymphocytes. However, cleavage at R781 was evident in ABC-DLBCL cells such as OCI-Ly3, HBL-1. HBL-1 cells with induced expression of catalytically-inactive MALT1&#95;C464A or cleavage-defective MALT1&#95;R781L exhibited characteristic of retarded-growth. These findings suggested that cleavage at R781 of MALT1 played a role in the survival of ABC-DLBCL cells.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- B-Cell CLL-Lymphoma 10 Protein genetics
B-Cell CLL-Lymphoma 10 Protein metabolism
HEK293 Cells
Humans
Interferon-gamma genetics
Interferon-gamma metabolism
Interleukin-2 genetics
Interleukin-2 metabolism
Jurkat Cells
Lymphoma, Large B-Cell, Diffuse genetics
Lymphoma, Large B-Cell, Diffuse pathology
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein genetics
NF-kappa B genetics
Neoplasm Proteins genetics
Lymphoma, Large B-Cell, Diffuse metabolism
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein metabolism
NF-kappa B metabolism
Neoplasm Proteins metabolism
Proteolysis
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 13
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 29953499
- Full Text :
- https://doi.org/10.1371/journal.pone.0199779