...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons
【24h】

A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons

机译：包含UBR盒基序并识别N-Degron的哺乳动物E3泛素里加斯家族。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A subset of proteins targeted by the N-end rule pathway bear degradation signals called N-degrons, whose determinants include destabilizing N-terminal residues. Our previous work identified mouse UBR1 and UBR2 as E3 ubiquitin ligases that recognize N-degrons. Such E3s are called N-recognins. We report here that while double-mutant UBR1?/? UBR2?/? mice die as early embryos, the rescued UBR1?/? UBR2?/? fibroblasts still retain the N-end rule pathway, albeit of lower activity than that of wild-type fibroblasts. An affinity assay for proteins that bind to destabilizing N-terminal residues has identified, in addition to UBR1 and UBR2, a huge (570 kDa) mouse protein, termed UBR4, and also the 300-kDa UBR5, a previously characterized mammalian E3 known as EDD/hHYD. UBR1, UBR2, UBR4, and UBR5 shared a ～70-amino-acid zinc finger-like domain termed the UBR box. The mammalian genome encodes at least seven UBR box-containing proteins, which we propose to call UBR1 to UBR7. UBR1?/? UBR2?/? fibroblasts that have been made deficient in UBR4 as well (through RNA interference) were significantly impaired in the degradation of N-end rule substrates such as the Sindbis virus RNA polymerase nsP4 (bearing N-terminal Tyr) and the human immunodeficiency virus type 1 integrase (bearing N-terminal Phe). Our results establish the UBR box family as a unique class of E3 proteins that recognize N-degrons or structurally related determinants for ubiquitin-dependent proteolysis and perhaps other processes as well.
机译：N端规则途径靶向的蛋白质的一个子集带有称为N-degrons的降解信号，其决定因素包括不稳定的N末端残基。我们以前的工作将小鼠UBR1和UBR2识别为识别N-degrons的E3泛素连接酶。这种E3被称为N-recognins。我们在此报告，虽然双突变 UBR1 ？/？ UBR2 ？/？小鼠死于早期胚胎，被拯救的 UBR1 ？/？ UBR2 ？/？成纤维细胞仍保留N端规则途径，尽管活性低于野生型成纤维细胞。除UBR1和UBR2外，还对与不稳定的N末端残基结合的蛋白质进行了亲和力测定，发现了巨大的（570 kDa）小鼠蛋白质，称为UBR4，以及300 kDa的UBR5，先前被称为哺乳动物的E3，称为E3 EDD / hHYD。 UBR1，UBR2，UBR4和UBR5共享一个约70个氨基酸的锌指状结构域，称为UBR盒。哺乳动物基因组编码至少七个包含UBR盒的蛋白质，我们建议将其称为UBR1至UBR7。 UBR1 ？/？ UBR2 ？/？成纤维细胞也被制成UBR4缺陷（通过RNA干扰） ）在S底比斯病毒RNA聚合酶nsP4（带有N端Tyr）和人类免疫缺陷病毒1型整合酶（带有N端Phe）的N端规则底物的降解中受到了显着损害。我们的研究结果将UBR box家族确立为一种独特的E3蛋白类别，可以识别N-degrons或与泛素相关的蛋白水解以及其他过程的结构相关决定簇。

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