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Yeast Derlin Dfm1 interacts with Cdc48 and functions in ER homeostasis
Author(s) -
Sato Brian K.,
Hampton Randolph Y.
Publication year - 2006
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.1407
Subject(s) - endoplasmic reticulum associated protein degradation , biology , saccharomyces cerevisiae , aaa proteins , unfolded protein response , endoplasmic reticulum , yeast , microbiology and biotechnology , ubiquitin , biochemistry , atpase , gene , enzyme
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 © 2006 John Wiley & Sons, Ltd.