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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
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TAK1 lessens the activity of the paracaspase MALT1 during T cell receptor signaling

Carolina Alves Nicolau1, Julie Gavard2, Nicolas Bidère1

  • 1CRCINA, Team SOAP, INSERM, CNRS, Université de Nantes, Université d'Angers, IRS-UN blg, Room 405, 8 quai Moncousu, Nantes 44007, France; L'Héma-NexT, i-Site NexT, Nantes, France; GDR3697 Micronit, CNRS, Nantes, France.

Cellular Immunology
|May 11, 2020
PubMed

Insights

Transforming growth factor beta-activated kinase 1 (TAK1) inhibition enhances MALT1 substrate processing and CARMA1-BCL10-MALT1 (CBM) complex assembly. This suggests TAK1 negatively regulates CBM complex activity in T/B lymphocytes.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The CARMA1-BCL10-MALT1 (CBM) complex is essential for coupling antigen receptors to Nuclear Factor κB (NF-κB) activation in T and B lymphocytes.
  • MALT1, a key component of the CBM complex, functions as both an adaptor and a protease, regulating NF-κB activity and lymphocyte activation.

Purpose of the Study:

  • To investigate the regulatory role of transforming growth factor beta-activated kinase 1 (TAK1) in the CBM complex signaling pathway.
  • To elucidate how TAK1 influences MALT1 processing and CBM complex assembly.

Main Methods:

  • Chemical inhibition and siRNA-based silencing of TAK1.
  • Analysis of MALT1 substrate processing.
  • Assessment of CBM complex assembly and MALT1 ubiquitination.

Main Results:

  • Inhibition or silencing of TAK1 enhanced the processing of MALT1 substrates.
  • TAK1 inhibition led to increased CBM complex assembly.
  • MALT1 ubiquitination was augmented upon TAK1 inhibition.

Conclusions:

  • TAK1 acts as a negative regulator of the CBM complex.
  • TAK1 may initiate a negative feedback loop to fine-tune CBM complex activity and NF-κB signaling in lymphocytes.
Keywords:
CBM complexLymphocyteMALT1NF-κBSignalingTAK1

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