TAK1 lessens the Activity of the Paracaspase MALT1 during T cell Receptor Signaling

Carolina Alves Nicolau (1, 2, 3) , Julie Gavard (1, 2, 3, 4) , Nicolas Bidère (1, 2, 3)

1 CRCINA-ÉQUIPE 15 - Signaling in Oncogenesis, Angiogenesis and Permeability
2 i-Site NexT - L’Héma-NexT [UNIV Nantes]
3 CNRS GDR 3697 Micronit - Microenvironnement des niches tumorales
4 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]

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.

Mots clés: NF-κB; Signaling; Lymphocyte; TAK1; MALT1; CBM complex

Domaines: Cancer

Carolina Alves Nicolau, Julie Gavard, Nicolas Bidère. TAK1 lessens the Activity of the Paracaspase MALT1 during T cell Receptor Signaling. Cellular Immunology, 2020, pp.104115. ⟨10.1016/j.cellimm.2020.104115⟩. ⟨inserm-02558368⟩