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Updated: Feb 3, 2026
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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
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MALT1 activation by TRAF6 needs neither BCL10 nor CARD11
Maureen Bardet1, Thomas Seeholzer2, Adeline Unterreiner1
1Novartis Institutes for BioMedical Research, Novartis Campus, Basel, Switzerland.
Biochemical and Biophysical Research Communications
|October 20, 2018
Summary
The E3-ligase TRAF6 can activate Mucosa Associated Lymphoid Tissue Lymphoma Translocation protein 1 (MALT1) protease activity independently of the canonical CBM complex. TRAF6 activation of MALT1 does not require CARD11 or BCL10.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Mucosa Associated Lymphoid Tissue Lymphoma Translocation protein 1 (MALT1) is a key signaling molecule in lymphocytes.
- MALT1 activation typically involves the CARMA1-BCL10-MALT1 (CBM) complex.
- Alternative MALT1 activation pathways, including those involving TRAF6, are being investigated.
Purpose of the Study:
- To investigate the role of TRAF6 in MALT1 activation.
- To determine if TRAF6-mediated MALT1 activation is dependent on the canonical CBM complex components (CARD11 and BCL10).
Main Methods:
- CRISPR/Cas9 gene editing was used to generate Jurkat T-cell lines with knock-outs for CARD11 or BCL10.
- MALT1 activation was assessed in response to T-cell stimulation and ectopic TRAF6 expression.
Main Results:
- TRAF6 was dispensable for CARD11/BCL10-dependent MALT1 activation during T-cell stimulation.
- Ectopically expressed TRAF6 induced MALT1 activity in Jurkat T-cells lacking CARD11 or BCL10.
- TRAF6-mediated MALT1 activation occurred independently of CARD11 and BCL10.
Conclusions:
- TRAF6 can activate MALT1 protease activity through a non-canonical pathway.
- This TRAF6-dependent pathway bypasses the requirement for the CBM complex, CARD11, and BCL10.
- These findings reveal a novel mechanism for MALT1 activation in lymphocyte signaling.
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