Role of the ubiquitin-selective CDC48UFD1/NPL4 chaperone (segregase) in ERAD of OLE1 and other substrates
Role of the ubiquitin-selective CDC48UFD1/NPL4 chaperone (segregase) in ERAD of OLE1 and other substrates
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DOI：
10.1093/emboj/21.4.615
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发表时间：
2002-02-15
期刊：
影响因子：
11.4
通讯作者：
Jentsch, S
中科院分区：
文献类型：
--
作者：
Braun, S;Matuschewski, K;Jentsch, S
酵母的OLE途径调节ER结合酶Delta-9脂肪酸去饱和酶OLE 1的丰度，从而控制不饱和脂肪酸池和膜流动性。以前，我们表明，这一途径是由泛素/蛋白酶体系统的精细调控。该途径的激活涉及膜结合转录因子的蛋白酶体加工以及随后通过CDC 48（UFD 1/NPL 4）（一种泛素选择性伴侣样酶）将裂解的泛素化转录因子从其伴侣分子中动员出来。在这里，我们报告说，OLE 1蛋白本身是自然短命的，并通过泛素/蛋白酶体依赖性ER相关降解（ERAD）降解。我们发现，CDC 48（UFD 1/NPL 4）通过介导OLE 1的ERAD在OLE途径中发挥第二作用。有趣的是，其他ERAD底物也需要CDC 48 UFD 1/NPL 4进行降解，表明这种酶是ERAD机制的一种新的组成成分。我们提出，CDC 48（UFD 1/NPL 4）作为分离酶的功能，从未修饰的合作伙伴释放泛素化蛋白。
The OLE pathway of yeast regulates the abundance of the ER-bound enzyme Delta-9 fatty acid desaturase OLE1, thereby controlling unsaturated fatty acid pools and membrane fluidity. Previously, we showed that this pathway is exquisitely regulated by the ubiquitin/proteasome system. Activation of the pathway involves proteasomal processing of a membrane-bound transcription factor and the subsequent mobilization of the cleaved, ubiquitylated transcription factor from its partner molecule by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone-like enzyme. Here we report that the OLE1 protein itself is naturally short-lived and is degraded by ubiquitin/proteasome-dependent ER-associated degradation (ERAD). We found that CDC48(UFD1/NPL4) plays a second role in the OLE pathway by mediating ERAD of OLE1 Intriguingly, other ERAD substrates also require CDC48UFD1/NPL4 for degradation, indicating that this enzyme is a novel, constitutive component of the ERAD machinery. We propose that CDC48(UFD1/NPL4) functions as a segregase that liberates ubiquitylated proteins from non-modified partners.