Selenoprotein S-dependent Selenoprotein K Binding to p97(VCP) Protein Is Essential for Endoplasmic Reticulum-associated Degradation.
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 SelS-dependent, and the resulting ERAD complex (SelS-p97(VCP)-SelK) plays an important role in ERAD and ER stress.
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and.
Jea Hwang
JH
Lee
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and.
Ki Jun
KJ
Park
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and.
Jun Ki
JK
Jang
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and.
Yeong Ha
YH
Jeon
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and.
Kwan Young
KY
Ko
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and.
Joon Hyun
JH
Kwon
the Departments of Biochemistry and Biomedical Science, Research Center for Aging and Geriatrics, Research Institute of Medical Science, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
Seung-Rock
SR
Lee
From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-713, Republic of Korea and ickkim@korea.ac.kr.
Ick Young
IY
Kim
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D051140:Selenoproteins / Q000378:metabolism*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; C000597149:selenoprotein K, mouse; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse
ER-associated degradation; endoplasmic reticulum stress (ER stress); p97(VCP); protein-protein interaction; selenium; selenoprotein