• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Malt1 and cIAP2-Malt1 as effectors of NF-kappa B activation: Kissing cousins or distant relatives?
【24h】

Malt1 and cIAP2-Malt1 as effectors of NF-kappa B activation: Kissing cousins or distant relatives?

机译：Malt1和cIAP2-Malt1作为NF-κB激活的效应子：亲吻表亲还是远亲？

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Malt1 is a multi-domain cytosolic signaling molecule that was originally identified as the target of recurrent translocations in a large fraction of MALT lymphomas. The product of this translocation is a chimeric protein in which the N-terminus is contributed by the apoptosis inhibitor, cIAP2, and the C-terminus is contributed by Malt1. Early studies suggested that Malt1 is an essential intermediate in antigen receptor activation of NF-kappa B, and that the juxtaposition of the cIAP2 N-terminus and the Malt1 C-terminus results in deregulation of Malt1 NF-kappa B stimulatory activity. Initial experimental data further suggested that the molecular mechanisms of Malt1- and cIAP-Malt1-mediated NF-kappa B activation were quite similar. However, a number of more recent studies of both Malt1 and cIAP2-Malt1 now reveal that these proteins influence NF-kappa B activation by multiple distinct mechanisms, several of which are non-overlapping. Currently available data suggest a revised model in which cIAP2-Malt1 induces NF-kappa B activation via a mechanism that depends equally on domains contributed by cIAP2 and Malt1, which confer spontaneous oligomerization activity, polyubiquitin binding, proteolytic activity, and association with and activation of TRAF2 and TRAF6 at several independent binding sites. By contrast, emerging data suggest that the wild-type Malt1 protein uniquely contributes to NF-kappa B activation primarily through the control of two proteolytic cleavage mechanisms. Firstly, Malt1 directly cleaves and inactivates A20, a negative regulator of the antigen receptor-to-NF-kappa B pathway. Secondly, Malt1 interacts with caspase-8, inducing caspase-8 cleavage of c-FLIPL, initiating a pathway that contributes to activation of the I kappa B kinase (IKK) complex. Furthermore, data suggest that Malt1 plays a more limited and focused role in antigen receptor activation of NF-kappa B, serving to augment weak antigen signals and stimulate a defined subset of NF-kappa B dependent responses. Thus, the potent activation of NF-kappa B by cIAP2-Malt1 contrasts with the more subtle role of Malt1 in regulating specific NF-kappa B responses downstream of antigen receptor ligation. Published by Elsevier Inc.
机译：Malt1是一个多域胞质信号分子，最初被确定为大部分MALT淋巴瘤复发易位的靶标。这种易位的产物是一种嵌合蛋白，其中N端由凋亡抑制剂cIAP2贡献，而C端由Malt1贡献。早期研究表明，Malt1是NF-κB抗原受体激活中必不可少的中间体，而cIAP2 N末端和Malt1 C末端的并置会导致Malt1NF-κB刺激活性的失调。最初的实验数据进一步表明，Malt1和cIAP-Malt1介导的NF-κB活化的分子机制非常相似。但是，Malt1和cIAP2-Malt1的许多最新研究现在表明，这些蛋白质通过多种不同的机制影响NF-κB的活化，其中一些是不重叠的。目前可获得的数据表明，经过修订的模型中cIAP2-Malt1通过同样依赖于cIAP2和Malt1贡献的域的机制诱导NF-κB活化，赋予了自发寡聚活性，多聚泛素结合，蛋白水解活性以及与之结合和激活TRAF2和TRAF6位于几个独立的结合位点。相比之下，新兴数据表明，野生型Malt1蛋白主要通过两种蛋白水解切割机制的控制来独特地促进NF-κB的活化。首先，Malt1直接裂解并灭活抗原受体到NF-κB通路的负调节剂A20。其次，Malt1与caspase-8相互作用，诱导c-FLIPL的caspase-8切割，从而启动一条有助于激活IκB激酶（IKK）复合物的途径。此外，数据表明，Malt1在NF-κB的抗原受体激活中发挥更有限和集中的作用，用于增强弱抗原信号并刺激NF-κB依赖性反应的确定子集。因此，cIAP2-Malt1对NF-κB的有效激活与Malt1在调节抗原受体连接下游的特定NF-κB反应中更微妙的作用形成对比。由Elsevier Inc.发布

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号