UBXD1 is a VCP-interacting protein that is involved in ER-associated degradation
UBXD1 is a VCP-interacting protein that is involved in ER-associated degradation
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DOI：
10.1016/j.bbrc.2009.03.012
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发表时间：
2009-05-01
影响因子：
3.1
通讯作者：
Tsuji, Akihiko
中科院分区：
文献类型：
--
作者：
Nagahama, Masami;Ohnishi, Machi;Tsuji, Akihiko
AAA ATP酶VCP及其酵母直向同源物Cdc 48。在与Ufd 1-NpI 4异源二聚体作为接头的复合物中，在内质网相关降解（ERAD）中发挥重要作用。几种含有UBX结构域的蛋白质通过结合VCP/Cdc 48和其他ERAD组分如泛素连接酶来将泛素化底物募集到VCP/Cdc 48。在这里，我们表明，哺乳动物UBXD 1是一个额外的UBX结构域的蛋白质参与ERAD过程。UBXD 1是一种与VCP和Derlin-1相互作用的胞质蛋白。UBXD 1在细胞中的过表达导致Ufd 1从VCP选择性解离，导致ERAD抑制突变型囊性纤维化跨膜传导调节因子（CFFR）降解。此外，通过RNA干扰消除内源性UBXD 1蛋白也导致CFFR降解缺陷。总的来说，这些研究结果表明，UBXD 1是ERAD的调节成分，可以调节接头结合VCP。(C)2009 Elsevier Inc. All rights reserved.
AAA ATPase VCP and its yeast ortholog Cdc48. in a complex with the Ufd1-NpI4 heterodimer as an adaptor, play an essential role in endoplasmic reticulum-associated degradation (ERAD). Several UBX domain-containing proteins function to recruit ubiquitylated Substrates to VCP/Cdc48 by binding both VCP/Cdc48 and other ERAD components such as ubiquitin ligases. Here we show that mammalian UBXD1 is an additional UBX domain-containing protein involved in the ERAD process. UBXD1 is a cytosolic protein that interacts with VCP and Derlin-1. Overexpression of UBXD1 in cells Causes selective dissociation of Ufd1 from VCP, resulting in inhibition of mutant cystic fibrosis transmembrane conductance regulator (CFFR) degradation by ERAD. Additionally, depletion of endgenous UBXD1 protein by RNA interference also results in a defect in CFFR degradation. Collectively, these findings suggest that UBXD1 is a regulatory component of ERAD that may modulate the adaptor binding to VCP. (C) 2009 Elsevier Inc. All rights reserved.