CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis.
CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis.
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DOI：
10.3389/fimmu.2018.01887
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发表时间：
2018
影响因子：
7.3
通讯作者：
McAllister-Lucas LM
中科院分区：
文献类型：
--
作者：
McAuley JR;Freeman TJ;Ekambaram P;Lucas PC;McAllister-Lucas LM
CARMA - Bcl10 - MALT1 （CBM）信号小体是一种细胞内蛋白复合物，由CARMA支架蛋白、Bcl10连接蛋白和MALT1蛋白酶组成。这种复合体最初被发现是因为编码其成分的基因在淋巴恶性肿瘤中是突变和染色体易位的目标。我们现在知道，CBM信号体通过介导促炎、促存活的NF-κB转录因子的抗原受体依赖性激活，在正常淋巴细胞功能中起着至关重要的作用，并且这种信号复合物的失调促进了b细胞淋巴瘤的发生。最近，我们和其他人已经证明CBM信号体也在免疫系统外的细胞中起作用，包括在几种实体肿瘤中。虽然CARMA1（也称为CARD11）主要在淋巴组织中表达，但相关的支架蛋白CARMA3 （CARD10）在多种细胞类型中更广泛表达并参与含有CARMA3的CBM复合物。含有carma3的CBM复合物作用于特异性G蛋白偶联受体（gpcr）和/或生长因子受体酪氨酸激酶（rtk）的下游。由于GPCRs和/或RTKs的不适当表达和激活是几种实体肿瘤发病机制的基础，因此现在人们对阐明carma3介导的细胞信号在这些恶性肿瘤中的作用非常感兴趣。在这里，我们总结了导致我们目前对CARMA3在实体肿瘤生物学中的作用的理解的关键发现，并强调了我们目前在知识上的差距。
The CARMA–Bcl10–MALT1 (CBM) signalosome is an intracellular protein complex composed of a CARMA scaffolding protein, the Bcl10 linker protein, and the MALT1 protease. This complex was first recognized because the genes encoding its components are targeted by mutation and chromosomal translocation in lymphoid malignancy. We now know that the CBM signalosome plays a critical role in normal lymphocyte function by mediating antigen receptor-dependent activation of the pro-inflammatory, pro-survival NF-κB transcription factor, and that deregulation of this signaling complex promotes B-cell lymphomagenesis. More recently, we and others have demonstrated that a CBM signalosome also operates in cells outside of the immune system, including in several solid tumors. While CARMA1 (also referred to as CARD11) is expressed primarily within lymphoid tissues, the related scaffolding protein, CARMA3 (CARD10), is more widely expressed and participates in a CARMA3-containing CBM complex in a variety of cell types. The CARMA3-containing CBM complex operates downstream of specific G protein-coupled receptors (GPCRs) and/or growth factor receptor tyrosine kinases (RTKs). Since inappropriate expression and activation of GPCRs and/or RTKs underlies the pathogenesis of several solid tumors, there is now great interest in elucidating the contribution of CARMA3-mediated cellular signaling in these malignancies. Here, we summarize the key discoveries leading to our current understanding of the role of CARMA3 in solid tumor biology and highlight the current gaps in our knowledge.
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MALT1 活性在卡波西肉瘤相关疱疹病毒潜伏期和原发性渗出性淋巴瘤生长中的作用
影响因子：
11.4
作者：
Bonsignore L;Passelli K;Pelzer C;Perroud M;Konrad A;Thurau M;Stürzl M;Dai L;Trillo-Tinoco J;Del Valle L;Qin Z;Thome M
通讯作者：
Thome M
影响因子：
6.1
作者：
Cianfrocca, Roberta;Tocci, Piera;Rosano, Laura
通讯作者：
Rosano, Laura
影响因子：
30.5
作者：
Coornaert, Beatrice;Baens, Mathijs;Beyaert, Rudi
通讯作者：
Beyaert, Rudi
影响因子：
4.8
作者：
Bertin, J;Guo, Y;Alnemri, ES
通讯作者：
Alnemri, ES
影响因子：
10.4
作者：
Crawley, J. T. B.;Zanardelli, S.;Lane, D. A.
通讯作者：
Lane, D. A.