• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Collagen matrix assembly is driven by the interaction of von Hippel|[ndash]|Lindau tumor suppressor protein with hydroxylated collagen IV alpha 2
【24h】

Collagen matrix assembly is driven by the interaction of von Hippel|[ndash]|Lindau tumor suppressor protein with hydroxylated collagen IV alpha 2

机译：von Hippel | nindau抑癌蛋白与羟基化胶原蛋白IV alpha 2的相互作用驱动胶原蛋白基质的组装

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

摘要

Inactivation of the von Hippel–Lindau (VHL) tumor suppressor gene predisposes to vascular tumor formation in several organs. VHL regulates two evolutionary conserved pathways: the targeting of hydroxylated hypoxia-inducible factor-α (HIF-α) for proteasomal degradation and the remodeling of extracellular matrix (ECM). The biochemical mechanisms of the ECM assembly pathway remain poorly defined. Here, we provide evidence supporting a biochemical role for VHL in ECM assembly. We show that VHL directly binds to the collagen IV alpha 2 (COL4A2) chain and that this interaction is necessary for its assembly into the ECM. The VHL–COL4A2 interaction is dependent on endoplasmic reticulum (ER)-mediated COL4A2 hydroxylation and independent of cytosolic, hypoxia regulated HIF-α-modifying enzymes. We find that the N-terminal tail of COL4A2 protrudes from the ER lumen into the cytosol where it is bound by VHL. Failure of VHL to interact with COL4A2 correlates with loss of collagen IV network formation in vitro and collagen IV remodeling in vivo. Our data suggest a HIF-α-independent role for the VHL–COL4A2 interaction in suppression of angiogenic tumor formation through collagen IV network assembly.
机译：von Hippel-Lindau（VHL）肿瘤抑制基因的失活易在多个器官中形成血管肿瘤。 VHL调节两个进化的保守途径：靶向羟基化的缺氧诱导因子-α（HIF-α）来降解蛋白酶体和重塑细胞外基质（ECM）。 ECM组装途径的生化机制仍然不清楚。在这里，我们提供证据支持VHL在ECM组装中的生化作用。我们显示VHL直接绑定到胶原蛋白IVα2（COL4A2）链，并且这种相互作用是其组装成ECM所必需的。 VHL–COL4A2相互作用取决于内质网（ER）介导的COL4A2羟基化，并且独立于胞质，缺氧调节的HIF-α-修饰酶。我们发现，COL4A2的N末端尾巴从ER内腔突出进入胞质溶胶，在此处被VHL结合。 VHL无法与COL4A2相互作用与体外胶原IV网络形成的丧失和体内胶原IV重塑有关。我们的数据表明，VHL-COL4A2相互作用在通过胶原蛋白IV网络组装抑制血管生成性肿瘤形成中具有HIF-α独立性。

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