Yeast Derlin Dfm1 interacts with Cdc48 and functions in ER homeostasis
Yeast Derlin Dfm1 interacts with Cdc48 and functions in ER homeostasis
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DOI：
10.1002/yea.1407
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发表时间：
2006-10-01
期刊：
影响因子：
2.6
通讯作者：
Hampton, Randolph Y.
中科院分区：
文献类型：
--
作者：
Sato, Brian K.;Hampton, Randolph Y.
最近的研究已经确定了Derlin-1，一种与AAA-ATP酶p97相关的蛋白质，并参与ER相关蛋白降解（ERAD）的后期步骤。Derlin-1有两个酿酒酵母同源物Der 1 p和Dfm 1 p。虽然Der 1 p已被广泛研究，但对Dfm 1 p知之甚少。因此，我们研究了Dfm 1 p在ERAD，ER稳态和与酵母p97同源Cdc 48 p的相互作用中的作用。Dfm 1 p不参与许多Der 1依赖性或非依赖性ERAD底物的降解，也不与ERAD中的Der 1 p或Sec 61 p冗余。然而，Dfm 1 p在ER稳态中起作用，因为Dfm 1 p缺失或过表达可刺激未折叠蛋白反应（UPR）。此外，Dfm 1 p相互作用的遗传和物理与Cdc 48 p，酵母p97同源物，这种相互作用需要一个8个氨基酸的序列中发现的Dfm 1 p的C-末端，我们称之为SHP盒。我们的遗传学研究与Dfm 1 p在ERAD中缺乏作用是一致的，但表明它参与了ER相关的Cdc 48 p作用，不同于逆易位。最后，序列分析表明Dfm 1 p的UPR相关功能和Cdc 48 p相互作用功能是分离的，表明该蛋白可能在细胞中具有多种作用。因此，Derlins和p97之间的相互作用在酵母和哺乳动物之间是保守的，尽管它在ERAD中的功能不是。此外，Dfm 1 p通过其SHP盒与Cdc 48 p相互作用，因此定义了与这种广泛使用的AAA-ATPase相互作用的新基序。版权所有（c）2006约翰威利父子有限公司。
Recent studies have identified Derlin-1, a protein that associates with the AAA-ATPase p97 and is implicated in late steps in ER-associated protein degradation (ERAD). Derlin-1 has two Saccharomyces cerevisiae homologues, Der1p and Dfm1p. While Der1p has been studied extensively, little is known about Dfm1p. Accordingly, we investigated the role of Dfm1p in ERAD, ER homeostasis and interactions with the yeast p97 homologue Cdc48p. Dfm1p was not involved in the degradation of a number of Der1-dependent or -independent ERAD substrates, neither was it redundant with either Der1p or Sec61p in ERAD. However, Dfm1p had a role in ER homeostasis, since Dfm1p loss or overexpression could stimulate the unfolded protein response (UPR). Furthermore, Dfm1p interacted both genetically and physically with Cdc48p, the yeast p97 homologue, and this interaction required an eight amino acid sequence found in the C-terminus of Dfm1p that we have termed the SHP box. Our genetic studies are consistent with the lack of a role for Dfm1p in ERAD, but indicate it participates in ER-related Cdc48p actions distinct from retrotranslocation. Finally, sequence analysis indicated that the UPR-related and Cdc48p interaction functions of Dfm1p could be separated, implying this protein probably has numerous actions in the cell. Thus, the interaction between Derlins and p97 is conserved between yeast and mammals, although its function in ERAD is not. Furthermore, Dfm1p interacts with Cdc48p through its SHP boxes, and so defines a new motif for interaction with this widely-employed AAA-ATPase. Copyright (c) 2006 John Wiley & Sons, Ltd.