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.

中文翻译：

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TAK1在T细胞受体信号传导过程中降低了半胱氨酸蛋白酶MALT1的活性。

CARMA1-BCL10-MALT1（CBM）复合物将抗原受体与T / B淋巴细胞中核因子κB（NF-κB）转录因子的激活偶联。在该信号小体中，MALT1对半胱天冬酶具有双重作用：它是信号转导至NF-κB信号的关键衔接子，是一种可调节NF-κB活性和淋巴细胞活化的蛋白酶。尽管微妙的泛素化和磷酸化编排精心编排了CBM，但仍不清楚这种复合物和MALT1酶的调控精确度。在这里，我们报告说，转化生长因子β活化激酶1（TAK1）（NF-κB激活所需的CBM复合物的已知伴侣）的化学抑制或基于siRNA的沉默增强了MALT1底物的加工。我们进一步表明，当抑制TAK1时，CBM的组装以及MALT1的泛素化作用都增加了。因此，TAK1可能会启动一个负反馈回路来微调CBM复杂度活动。