Selenoprotein S-dependent selenoprotein K binding to p97(VCP) protein is essential for endoplasmic reticulum-associated degradation

Jea Hwang Lee, Ki Jun Park, Jun Ki Jang, Yeong Ha Jeon, Kwan Young Ko, Joon Hyun Kwon, Seung Rock Lee, Ick Young Kim

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)29941-29952
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number50
DOIs
Publication statusPublished - 2015 Dec 11

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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