TY - JOUR
T1 - Selenoprotein S-dependent selenoprotein K binding to p97(VCP) protein is essential for endoplasmic reticulum-associated degradation
AU - Lee, Jea Hwang
AU - Park, Ki Jun
AU - Jang, Jun Ki
AU - Jeon, Yeong Ha
AU - Ko, Kwan Young
AU - Kwon, Joon Hyun
AU - Lee, Seung Rock
AU - Kim, Ick Young
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/12/11
Y1 - 2015/12/11
N2 - Cytosolic valosin-containing protein (p97(VCP)) is translocated to the ER membrane by binding to selenoprotein S (SelS), which is an ER membrane protein, during endoplasmic reticulum-associated degradation (ERAD). Selenoprotein K (SelK) is another known p97(VCP)-binding selenoprotein, and the expression of both SelS and SelK is increased under ER stress. To understand the regulatory mechanisms of SelS, SelK, and p97(VCP) during ERAD, the interaction of the selenoproteins with p97(VCP) was investigated using N2a cells and HEK293 cells. Both SelS and SelK co-precipitated with p97(VCP). However, the association between SelS and SelK did not occur in the absence of p97(VCP). SelS had the ability to recruit p97(VCP) to the ER membrane but SelK did not. The interaction between SelK and p97(VCP) did not occur in SelS knockdown cells, whereas SelS interacted with p97(VCP) in the presence or absence of SelK. These results suggest that p97(VCP) is first translocated to the ER membrane via its interaction with SelS, and then SelK associates with the complex on the ER membrane. Therefore, the interaction between SelK and p97(VCP) is SelSdependent, and the resulting ERAD complex (SelS-p97(VCP)- SelK) plays an important role in ERAD and ER stress.
AB - Cytosolic valosin-containing protein (p97(VCP)) is translocated to the ER membrane by binding to selenoprotein S (SelS), which is an ER membrane protein, during endoplasmic reticulum-associated degradation (ERAD). Selenoprotein K (SelK) is another known p97(VCP)-binding selenoprotein, and the expression of both SelS and SelK is increased under ER stress. To understand the regulatory mechanisms of SelS, SelK, and p97(VCP) during ERAD, the interaction of the selenoproteins with p97(VCP) was investigated using N2a cells and HEK293 cells. Both SelS and SelK co-precipitated with p97(VCP). However, the association between SelS and SelK did not occur in the absence of p97(VCP). SelS had the ability to recruit p97(VCP) to the ER membrane but SelK did not. The interaction between SelK and p97(VCP) did not occur in SelS knockdown cells, whereas SelS interacted with p97(VCP) in the presence or absence of SelK. These results suggest that p97(VCP) is first translocated to the ER membrane via its interaction with SelS, and then SelK associates with the complex on the ER membrane. Therefore, the interaction between SelK and p97(VCP) is SelSdependent, and the resulting ERAD complex (SelS-p97(VCP)- SelK) plays an important role in ERAD and ER stress.
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U2 - 10.1074/jbc.M115.680215
DO - 10.1074/jbc.M115.680215
M3 - Article
C2 - 26504085
AN - SCOPUS:84949662465
VL - 290
SP - 29941
EP - 29952
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 50
ER -