L-CBM signaling in lymphocyte development and function.
L-CBM signaling in lymphocyte development and function.
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DOI：
10.2147/jbm.s9772
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发表时间：
2010
影响因子：
2
通讯作者：
Yoshida H
中科院分区：
文献类型：
--
作者：
Hara H;Iizasa E;Nakaya M;Yoshida H
核因子-κB（NF-κB）在淋巴细胞的活化和存活中起着重要作用。因此，NF-κB是获得性免疫的关键，但NF-κB信号转导的失调导致炎性疾病和淋巴瘤发生。越来越多的证据表明，粘膜相关淋巴组织（MALT）淋巴瘤相关分子，B细胞淋巴瘤10（BCL 10）和MALT淋巴瘤易位基因1（MALT 1）是NF-κB和丝裂原活化蛋白激酶（MAPK）活化的重要信号成分，由免疫受体酪氨酸活化基序（ITAM）偶联受体介导，参与先天性和适应性免疫。CARMA 1（也称为CARD 11和Bimp 3）是ITAM介导的信号传导的关键调节因子，因为它在淋巴谱系细胞如T、B、自然杀伤（NK）和自然杀伤T（NKT）细胞中与BCL 10-MALT 1形成复合物，称为淋巴CARMA 1-BCL 10-MALT 1（L-CBM）复合物。本文就L-CBM复合物的分子生物学功能和信号调节机制作一综述，并对其在疾病发展中的作用和作为治疗靶点的潜力作进一步讨论。
The nuclear factor-κB (NF-κB) plays a central role in the activation and survival of lymphocytes. NF-κB, therefore, is pivotal for acquired immunity, but the dysregulation of NF-κB signaling leads to inflammatory diseases and lymphomagenesis. Accumulating evidence has demonstrated that the mucosa-associated lymphoid tissue (MALT) lymphoma-related molecules, B-cell lymphoma 10 (BCL10) and MALT-lymphoma-translocation gene1 (MALT1), are essential signaling components for NF-κB and mitogen-activated protein kinase (MAPK) activation, mediated by the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors involved in both innate and adaptive immunity. CARMA1 (also referred to as CARD11 and Bimp3) is a crucial regulator for ITAM-mediated signaling as it forms a complex with BCL10-MALT1 in lymphoid lineage cells such as T, B, natural killer (NK), and natural killer T (NKT) cells, known as the lymphoid CARMA1-BCL10-MALT1 (L-CBM) complex. In this review, recent understanding of the molecular and biological functions and the signal regulation mechanisms of the L-CBM complex are described and its role in disease development and potential as a therapeutic target is further discussed.