从黏膜相关淋巴组织淋巴瘤到 CBM 信号体：三十年的发现历程。
From MALT lymphoma to the CBM signalosome: three decades of discovery.
机构信息
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
出版信息
Cell Cycle. 2011 Aug 1;10(15):2485-96. doi: 10.4161/cc.10.15.16923.
Abstract
The advent of molecular cytogenetics has led to the elucidation of genetic abnormalities that cause various congenital and oncological disorders. In B cell lymphoma, for example, a number of chromosomal translocations have been identified in and associated with the etiology of specific subtypes of lymphoma. Several recurrent chromosomal translocations have been identified in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Cloning and characterization of the products of three mutually exclusive translocation breakpoints found in MALT lymphoma led to the discovery of a novel NF-κB-activating complex comprising the CARMA, Bcl10, and MALT1 proteins. This "CBM signalosome" acts downstream of the antigen receptors in lymphocytes as well as a number of non-lymphoid cell-surface receptors involved in a variety of biological processes. CBM signalosome activity is important for normal cellular functions and is perturbed in neoplastic and inflammatory disorders, making it a viable target for novel therapeutic design.
摘要
分子细胞遗传学的出现导致了对导致各种先天性和肿瘤疾病的遗传异常的阐明。例如，在 B 细胞淋巴瘤中，已经确定了一些与特定淋巴瘤亚型的病因相关的染色体易位。在黏膜相关淋巴组织（MALT 淋巴瘤）的结外边缘区 B 细胞淋巴瘤中已经确定了几种反复出现的染色体易位。对 MALT 淋巴瘤中三个相互排斥的易位断点产物的克隆和特征描述导致了发现一种新型的 NF-κB 激活复合物，该复合物包含 CARMA、Bcl10 和 MALT1 蛋白。这个“CBM 信号体”在淋巴细胞中的抗原受体以及参与多种生物学过程的许多非淋巴细胞表面受体下游起作用。CBM 信号体的活性对于正常细胞功能很重要，并且在肿瘤和炎症性疾病中受到干扰，使其成为新型治疗设计的可行靶标。
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