Biogem, Via Camporeale, Ariano Irpino (AV), Italy.
Dipartimento di Scienze e Tecnologie, Università del Sannio, Via Port' Arsa 10, Benevento, Italy.
FEBS Open Bio. 2015 Feb 4;5:175-81. doi: 10.1016/j.fob.2015.01.007. eCollection 2015.
The complexes formed by BCL10, MALT1 and members of the family of CARMA proteins have recently been the focus of much attention because they represent a key mechanism for regulating activation of the transcription factor NF-κB. Here, we report the functional characterization of a novel isoform of BCL10 in the trout Oncorhynchus mykiss, which we named tBCL10. tBCL10 dimerizes, binds to components of the CBM complex and forms cytoplasmic filaments. Functionally, tBCL10 activates NF-κB transcription factor and is inhibited by the deubiquitinating enzyme A20. Finally, depletion experiments indicate that tBCL10 can functionally replace the human protein. This work demonstrates the evolutionary conservation of the mechanism of NF-κB activation through the CBM complex, and indicates that the rainbow trout O . mykiss can serve as a model organism to study this pathway.
BCL10、MALT1 和 CARMA 蛋白家族成员形成的复合物最近受到了广泛关注，因为它们代表了调节转录因子 NF-κB 激活的关键机制。在这里，我们报告了在虹鳟鱼 Oncorhynchus mykiss 中一种新型 BCL10 同工型的功能特征，我们将其命名为 tBCL10。tBCL10 二聚化，与 CBM 复合物的组成部分结合，并形成细胞质纤维。功能上，tBCL10 激活 NF-κB 转录因子，并被去泛素化酶 A20 抑制。最后，耗尽实验表明 tBCL10 可以替代人类蛋白发挥功能。这项工作证明了通过 CBM 复合物激活 NF-κB 的机制在进化上是保守的，并表明虹鳟鱼 O. mykiss 可以作为研究该途径的模式生物。
