...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Apoptosis >The ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 protect cells against TNFα- and FasL-induced apoptosis by interacting with caspase-8
【24h】

The ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 protect cells against TNFα- and FasL-induced apoptosis by interacting with caspase-8

机译：1型和2型单纯疱疹病毒的核糖核苷酸还原酶R1亚基通过与caspase-8相互作用保护细胞免受TNFα和FasL诱导的细胞凋亡

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

We previously reported that HSV-2 R1, the R1 subunit (ICP10; UL39) of herpes simplex virus type-2 ribonucleotide reductase, protects cells against apoptosis induced by the death receptor (DR) ligands tumor necrosis factor-alpha- (TNFα) and Fas ligand (FasL) by interrupting DR-mediated signaling at, or upstream of, caspase-8 activation. Further investigation of the molecular mechanism underlying HSV-2 R1 protection showed that extracellular-regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3-K)/Akt, NF-κB and JNK survival pathways do not play a major role in this antiapoptotic function. Interaction studies revealed that HSV-2 R1 interacted constitutively with caspase-8. The HSV-2 R1 deletion mutant R1(1-834)-GFP and Epstein–Barr virus (EBV) R1, which did not protect against apoptosis induced by DR ligands, did not interact with caspase-8, indicating that interaction is required for protection. HSV-2 R1 impaired caspase-8 activation induced by caspase-8 over-expression, suggesting that interaction between the two proteins prevents caspase-8 dimerization/activation. HSV-2 R1 bound to caspase-8 directly through its prodomain but did not interact with either its caspase domain or Fas-associated death domain protein (FADD). Interaction between HSV-2 R1 and caspase-8 disrupted FADD-caspase-8 binding. We further demonstrated that individually expressed HSV-1 R1 (ICP6) shares, with HSV-2 R1, the ability to bind caspase-8 and to protect cells against DR-induced apoptosis. Finally, as the long-lived Fas protein remained stable during the early period of infection, experiments with the HSV-1 UL39 deletion mutant ICP6∆ showed that HSV-1 R1 could be essential for the protection of HSV-1-infected cells against FasL.
机译：我们以前曾报道过HSV-2 R1，即单纯疱疹病毒2型核糖核苷酸还原酶的R1亚基（ICP10; UL39），可保护细胞免受死亡受体（DR）配体肿瘤坏死因子-α-（TNFα）和Fas配体（FasL）通过在caspase-8激活处或上游中断DR介导的信号传导来实现。对HSV-2 R1保护的分子机制的进一步研究表明，细胞外调节激酶1/2（ERK1 / 2），磷脂酰肌醇3-激酶（PI3-K）/ Akt，NF-κB和JNK的生存途径没有发挥作用。在这种抗凋亡功能中起主要作用。相互作用研究表明，HSV-2 R1与caspase-8组成型相互作用。 HSV-2 R1缺失突变体R1（1-834）-GFP和Epstein–Barr病毒（EBV）R1不能抵抗DR配体诱导的细胞凋亡，也不能与caspase-8相互作用，这表明保护。 HSV-2 R1破坏了由caspase-8过表达诱导的caspase-8激活，表明这两种蛋白之间的相互作用阻止了caspase-8二聚化/激活。 HSV-2 R1直接通过其前结构域与caspase-8结合，但不与其caspase结构域或Fas相关的死亡结构域蛋白（FADD）相互作用。 HSV-2 R1和caspase-8之间的相互作用破坏了FADD-caspase-8的结合。我们进一步证明，单独表达的HSV-1 R1（ICP6）与HSV-2 R1具有结合caspase-8并保护细胞免受DR诱导的细胞凋亡的能力。最后，由于长寿命的Fas蛋白在感染初期保持稳定，因此对HSV-1 UL39缺失突变体ICP6∆的实验表明，HSV-1 R1对于保护被HSV-1感染的细胞抵抗FasL可能是必不可少的。

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