Regulation of unfolded protein response via protein S-nitrosylation

Yu Ohkubo, Ryosuke Nakato, Takashi Uehara

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Nitric oxide (NO) plays a pivotal function in neurotransmission, vasodilation, proliferation, and apoptosis in various types of cells via protein S-nitrosylation. Previously we demonstrated that protein disulfide isomerase (PDI) is Snitrosylated in brains manifesting sporadic neurodegenerative diseases. This modification results in dysfunction of its enzymatic activity and consequently the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER). The aim of this study was to clarify the detailed function of NO on unfolded protein response (UPR) branches. We here found that the ER stress sensor IRE1α is S-nitrosylated. Interestingly, NO specifically abrogates ribonuclease activity, but not oligomerization or autophosphorylation of IRE1α. Site-directed mutagenesis revealed that Cys 931 and Cys951 in IRE1 are targets for S-nitrosylation. These mutants expressing in IRE1a knockout MEF showed a resistant role to the inhibition of nuclease activity by NO. Thus, we elucidated the effects of S-nitrosylation on ER stress sensors that mediate the UPR, and thus contribute to cell death pathways.

Original languageEnglish
Pages (from-to)801-804
Number of pages4
JournalYakugaku Zasshi
Volume136
Issue number6
DOIs
Publication statusPublished - 2016

Fingerprint

Unfolded Protein Response
Protein S
Nitric Oxide
Endoplasmic Reticulum Stress
Protein Disulfide-Isomerases
Protein Unfolding
Ribonucleases
Site-Directed Mutagenesis
Vasodilation
Synaptic Transmission
Endoplasmic Reticulum
Neurodegenerative Diseases
Cell Death
Apoptosis
Brain

Keywords

  • Apoptosis
  • Endoplasmic reticulum
  • Nitric oxide
  • S-nitrosylation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Regulation of unfolded protein response via protein S-nitrosylation. / Ohkubo, Yu; Nakato, Ryosuke; Uehara, Takashi.

In: Yakugaku Zasshi, Vol. 136, No. 6, 2016, p. 801-804.

Research output: Contribution to journalReview article

Ohkubo, Yu ; Nakato, Ryosuke ; Uehara, Takashi. / Regulation of unfolded protein response via protein S-nitrosylation. In: Yakugaku Zasshi. 2016 ; Vol. 136, No. 6. pp. 801-804.
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