Pro178 and Pro183 of selenoprotein S are essential residues for interaction with p97(VCP) during endoplasmic reticulum-associated degradation

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

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26 Citations (Scopus)


During endoplasmic reticulum (ER)-associated degradation, p97(VCP) is recruited to the ER membrane through interactions with transmembrane proteins, such as selenoprotein S (SelS), selenoprotein K (SelK), hrd1, and gp78. SelS has a single-spanning transmembrane domain and protects cells from ER stressinduced apoptosis t0068rough interaction with p97(VCP). The cytosolic tail of SelS consists of a coiled-coil domain, a putative VCP-interacting motif (VIM), and an unpronounced glycineand proline-rich secondary structure. To understand the regulatory mechanism of SelS during ER stress, we investigated the interaction of the protein with p97(VCP) using mouse neuroblastoma cells and human embryonic kidney 293 cells. The SelS expression level increased when ER stress was induced. In addition, the effect of ER stress was enhanced, and recruitment of p97(VCP) to the ER membrane was inhibited in SelS knockdown cells. The effect of SelS knockdown was rescued by ectopic expression of SelS U188C.p97(VCP) interacted with SelSU188Candwas recruited to the ER membrane. The expression of SelS[ΔVIM], which is a VIM deletion mutant of SelS, also showed both a recovery effect and an interaction with p97(VCP) in cells. However, mutants in which the proline residue positions 178 or 183 of SelS were changed to alanine or were deleted did not interact with p97(VCP). The proline mutants did not rescue ER stress in SelS knockdown cells. These results suggest that both Pro178 and Pro183 of SelS play important roles in the translocation of p97(VCP) to the ER membrane and protect cells from ER stress.

Original languageEnglish
Pages (from-to)13758-13768
Number of pages11
JournalJournal of Biological Chemistry
Issue number20
Publication statusPublished - 2014 May 16

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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