NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein
Abstract
Homocysteine-induced endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible key regulatory component of ER-associated degradation (ERAD) that has been implicated in insulin hypersecretion in diabetic mouse models. Herp expression is tightly regulated. Additionally, Herp is a highly labile protein and interacts with various proteins, which are characteristic features of ubiquitinated protein. Previously, we reported that ubiquitination is not required for Herp degradation. In addition, we found that the lysine residues of Herp (which are ubiquitinated by E3 ubiquitin ligase) are not sufficient for regulation of Herp degradation. In this study, we found that NAD(P)H quinone oxidoreductase 1 (NQO1)-mediated targeting of Herp to the proteasome was involved in Herp degradation. In addition, we found that Herp protein levels were markedly elevated in synoviolin-null cells. The E3 ubiquitin ligase synoviolin is a central component of ERAD and is involved in the degradation of nuclear factor E2-related factor-2 (Nrf2), which regulates cellular reactive oxygen species. Additionally, NQO1 is a target of Nrf2. Thus, our findings indicated that NQO1 could stabilize Herp protein expression via indirect regulation of synoviolin. -- Highlights: •Herp interacts with NQO1. •NQO1 regulates Herp degradation.
- Authors:
-
- Department of Neuroscience, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-Cho, Shiwagun, Iwate, 028-3603 (Japan)
- Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjyuku, Shinjyuku, Tokyo, Tokyo, 160-8402 (Japan)
- Publication Date:
- OSTI Identifier:
- 22598725
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 473; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; BENZOQUINONES; BIOLOGICAL STRESS; ENDOPLASMIC RETICULUM; HOMOCYSTEINE; INSULIN; LIGASES; LYSINE; MICE; NAD; OXIDOREDUCTASES
Citation Formats
Maeda, Tomoji, Tanabe-Fujimura, Chiaki, Fujita, Yu, Abe, Chihiro, Nanakida, Yoshino, Zou, Kun, Liu, Junjun, Liu, Shuyu, Nakajima, Toshihiro, and Komano, Hiroto. NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein. United States: N. p., 2016.
Web. doi:10.1016/J.BBRC.2016.04.057.
Maeda, Tomoji, Tanabe-Fujimura, Chiaki, Fujita, Yu, Abe, Chihiro, Nanakida, Yoshino, Zou, Kun, Liu, Junjun, Liu, Shuyu, Nakajima, Toshihiro, & Komano, Hiroto. NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein. United States. https://doi.org/10.1016/J.BBRC.2016.04.057
Maeda, Tomoji, Tanabe-Fujimura, Chiaki, Fujita, Yu, Abe, Chihiro, Nanakida, Yoshino, Zou, Kun, Liu, Junjun, Liu, Shuyu, Nakajima, Toshihiro, and Komano, Hiroto. 2016.
"NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein". United States. https://doi.org/10.1016/J.BBRC.2016.04.057.
@article{osti_22598725,
title = {NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein},
author = {Maeda, Tomoji and Tanabe-Fujimura, Chiaki and Fujita, Yu and Abe, Chihiro and Nanakida, Yoshino and Zou, Kun and Liu, Junjun and Liu, Shuyu and Nakajima, Toshihiro and Komano, Hiroto},
abstractNote = {Homocysteine-induced endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible key regulatory component of ER-associated degradation (ERAD) that has been implicated in insulin hypersecretion in diabetic mouse models. Herp expression is tightly regulated. Additionally, Herp is a highly labile protein and interacts with various proteins, which are characteristic features of ubiquitinated protein. Previously, we reported that ubiquitination is not required for Herp degradation. In addition, we found that the lysine residues of Herp (which are ubiquitinated by E3 ubiquitin ligase) are not sufficient for regulation of Herp degradation. In this study, we found that NAD(P)H quinone oxidoreductase 1 (NQO1)-mediated targeting of Herp to the proteasome was involved in Herp degradation. In addition, we found that Herp protein levels were markedly elevated in synoviolin-null cells. The E3 ubiquitin ligase synoviolin is a central component of ERAD and is involved in the degradation of nuclear factor E2-related factor-2 (Nrf2), which regulates cellular reactive oxygen species. Additionally, NQO1 is a target of Nrf2. Thus, our findings indicated that NQO1 could stabilize Herp protein expression via indirect regulation of synoviolin. -- Highlights: •Herp interacts with NQO1. •NQO1 regulates Herp degradation.},
doi = {10.1016/J.BBRC.2016.04.057},
url = {https://www.osti.gov/biblio/22598725},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 473,
place = {United States},
year = {Fri May 13 00:00:00 EDT 2016},
month = {Fri May 13 00:00:00 EDT 2016}
}