TAK1 lessens the activity of the paracaspase MALT1 during T cell receptor signaling

Cell Immunol. 2020 Jul:353:104115. doi: 10.1016/j.cellimm.2020.104115. Epub 2020 Apr 28.


The CARMA1-BCL10-MALT1 (CBM) complex couples antigen receptors to the activation of Nuclear Factor κB (NF-κB) transcription factors in T/B lymphocytes. Within this signalosome, the MALT1 paracaspase serves dual roles: it is a crucial adaptor for signal transduction to NF-κB signaling, and a protease that shapes NF-κB activity and lymphocyte activation. Although a subtle choreography of ubiquitination and phosphorylation orchestrate the CBM, how precisely this complex and MALT1 enzyme are regulated continue to be elucidated. Here, we report that the chemical inhibition or the siRNA-based silencing of transforming growth factor beta-activated kinase 1 (TAK1), a known partner of the CBM complex required for NF-κB activation, enhanced the processing of MALT1 substrates. We further show that the assembly of the CBM as well as the ubiquitination of MALT1 was augmented when TAK1 was inhibited. Thus, TAK1 may initiate a negative feedback loop to finely tune the CBM complex activity.

Keywords: CBM complex; Lymphocyte; MALT1; NF-κB; Signaling; TAK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • B-Lymphocytes / immunology
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • MAP Kinase Kinase Kinases / metabolism*
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein / metabolism*
  • Multiprotein Complexes / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Proteins / genetics
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism


  • Adaptor Proteins, Signal Transducing
  • Multiprotein Complexes
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factors
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein