Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation
Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation
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DOI：
10.1038/35050524
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发表时间：
2001-01-01
影响因子：
21.3
通讯作者：
Hampton, RY
中科院分区：
文献类型：
--
作者：
Bays, NW;Gardner, RG;Hampton, RY
在真核生物中，内质网相关降解 (ERAD) 在细胞质量控制和正常 ER 驻留蛋白的调节中发挥作用。 ERAD 通过泛素-蛋白酶体途径进行，其中泛素与蛋白质共价连接，靶向蛋白质进行蛋白酶体降解。泛素蛋白连接酶 (E3) 通过识别靶蛋白并启动其泛素化在此过程中发挥着至关重要的作用。在这里，我们表明 Hrd1p 与 Der3p 相同，是 ERAD 的 E3。 Hrd1p 是多种 ERAD 底物降解和泛素化所必需的，并与相关泛素结合酶 (E2) 发生物理关联。可溶性 Hrd1 融合蛋白在体外显示出 E3 活性 - 催化自身和测试蛋白的泛素化。在这种能力下，Hrd1p 对错误折叠的蛋白质有明显的偏好。我们还表明，Hrd1p 在体内发挥 E3 的作用，仅使用 Ubc7p 或 Ubc1p 来特异性编程 ERAD 底物的泛素化。
In eukaryotes, endoplasmic reticulum-associated degradation (ERAD) functions in cellular quality control and regulation of normal ER-resident proteins. ERAD proceeds by the ubiquitin-proteasome pathway, in which the covalent attachment of ubiquitin to proteins targets them for proteasomal degradation. Ubiquitin-protein ligases (E3s) play a crucial role in this process by recognizing target proteins and initiating their ubiquitination. Here we show that Hrd1p, which is identical to Der3p, is an E3 for ERAD. Hrd1p is required for the degradation and ubiquitination of several ERAD substrates and physically associates with relevant ubiquitin-conjugating enzymes (E2s). A soluble Hrd1 fusion protein shows E3 activity in vitro - catalysing the ubiquitination of itself and test proteins. In this capacity, Hrd1p has an apparent preference for misfolded proteins. We also show that Hrd1p functions as an E3 in vivo, using only Ubc7p or Ubc1p to specifically program the ubiquitination of ERAD substrates.