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首页> 外文期刊>Cellular immunology >Critical protein-protein interactions within the CARMA1-BCL10-MALT1 complex: Take-home points for the cell biologist
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Critical protein-protein interactions within the CARMA1-BCL10-MALT1 complex: Take-home points for the cell biologist

机译：Carma1-BCL10-MALT1复合物中的关键蛋白质 - 蛋白质相互作用：细胞生物学家的带家庭点

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摘要

The CBM complex, which is composed of the proteins CARMA1, BCL10, and MALT1, serves multiple pivotal roles as a mediator of T-cell receptor and B-cell receptor-dependent NF-kappa B induction and lymphocyte activation. CARMA1, BCL10, and MALT1 are each proto-oncoproteins and dysregulation of CBM signaling, as a result of somatic gain-of-function mutation or chromosomal translocation, is a hallmark of multiple lymphoid malignancies including Activated B-cell Diffuse Large B-cell Lymphoma. Moreover, loss-of-function as well as gain-of-function germline mutations in CBM complex proteins have been associated with a range of immune dysregulation syndromes. A wealth of detailed structural information has become available over the past decade through meticulous interrogation of the interactions between CBM components. Here, we review key findings regarding the biochemical nature of these protein-protein interactions which have ultimately led the field to a sophisticated understanding of how these proteins assemble into high-order filamentous CBM complexes. To date, approaches to therapeutic inhibition of the CBM complex for the treatment of lymphoid malignancy and/or auto-immunity have focused on blocking MALT1 protease function. We also review key studies relating to the structural impact of MALT1 protease inhibitors on key protein-protein interactions.
机译：CBM复合物由蛋白质CARMA1、BCL10和MALT1组成，在T细胞受体和B细胞受体依赖性NF-κB诱导和淋巴细胞活化中起着多个关键作用。CARMA1、BCL10和MALT1都是原癌蛋白，CBM信号的失调是由体细胞功能获得性突变或染色体易位引起的，是包括活化B细胞弥漫性大B细胞淋巴瘤在内的多种淋巴恶性肿瘤的标志。此外，CBM复合蛋白的功能丧失和功能获得种系突变与一系列免疫失调综合征有关。在过去的十年中，通过对CBM组件之间的相互作用进行细致的询问，可以获得大量详细的结构信息。在这里，我们回顾了有关这些蛋白质相互作用的生化性质的关键发现，这些发现最终使该领域对这些蛋白质如何组装成高阶丝状CBM复合物有了深入的了解。迄今为止，治疗性抑制CBM复合物治疗淋巴恶性肿瘤和/或自身免疫的方法主要集中在阻断MALT1蛋白酶功能。我们还回顾了与MALT1蛋白酶抑制剂对关键蛋白质相互作用的结构影响相关的关键研究。

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