4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.

p62, an adapter protein involved in selective autophagy, is mainly found in the cytoplasm under normal conditions. Because p62 has nuclear localization signal (NLS) and a nuclear export signal, it has been suggested that p62 shuttles between the nucleus and cytoplasm. We studied the effect of 4-hydr...

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Main Authors: Emi Kayama, Ning Baoshuo, Rinna Tatsuno, Kanako Nishi, Elsayed S I Mohammed, Yumi Abiko, Toru Yanagawa, Satoru Takahashi, Eiji Warabi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0316558
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author Emi Kayama
Ning Baoshuo
Rinna Tatsuno
Kanako Nishi
Elsayed S I Mohammed
Yumi Abiko
Toru Yanagawa
Satoru Takahashi
Eiji Warabi
author_facet Emi Kayama
Ning Baoshuo
Rinna Tatsuno
Kanako Nishi
Elsayed S I Mohammed
Yumi Abiko
Toru Yanagawa
Satoru Takahashi
Eiji Warabi
author_sort Emi Kayama
collection DOAJ
description p62, an adapter protein involved in selective autophagy, is mainly found in the cytoplasm under normal conditions. Because p62 has nuclear localization signal (NLS) and a nuclear export signal, it has been suggested that p62 shuttles between the nucleus and cytoplasm. We studied the effect of 4-hydroxy-nonenal (4-HNE), an endogenous lipid peroxidation product, on intracellular p62 distribution in mouse embryonic fibroblasts. We found that treatment of 4-HNE causes p62 translocation from the cytoplasm to the nucleus. Further analysis revealed that 4-HNE directly binds to exportin-1 (Xpo1), essential protein for nuclear export of various proteins. Further analysis 4-HNE enhanced intranuclear EGFP-NLS-CL1 degradation in a p62-dependent manner. Our results suggest that 4-HNE changes p62 localization to the nucleus by inhibiting Xpo1 and might affect intranuclear protein quality control.
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institution Kabale University
issn 1932-6203
language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-946a5d7b945f442fab2dc821cb39cd582025-02-07T05:30:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031655810.1371/journal.pone.03165584-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.Emi KayamaNing BaoshuoRinna TatsunoKanako NishiElsayed S I MohammedYumi AbikoToru YanagawaSatoru TakahashiEiji Warabip62, an adapter protein involved in selective autophagy, is mainly found in the cytoplasm under normal conditions. Because p62 has nuclear localization signal (NLS) and a nuclear export signal, it has been suggested that p62 shuttles between the nucleus and cytoplasm. We studied the effect of 4-hydroxy-nonenal (4-HNE), an endogenous lipid peroxidation product, on intracellular p62 distribution in mouse embryonic fibroblasts. We found that treatment of 4-HNE causes p62 translocation from the cytoplasm to the nucleus. Further analysis revealed that 4-HNE directly binds to exportin-1 (Xpo1), essential protein for nuclear export of various proteins. Further analysis 4-HNE enhanced intranuclear EGFP-NLS-CL1 degradation in a p62-dependent manner. Our results suggest that 4-HNE changes p62 localization to the nucleus by inhibiting Xpo1 and might affect intranuclear protein quality control.https://doi.org/10.1371/journal.pone.0316558
spellingShingle Emi Kayama
Ning Baoshuo
Rinna Tatsuno
Kanako Nishi
Elsayed S I Mohammed
Yumi Abiko
Toru Yanagawa
Satoru Takahashi
Eiji Warabi
4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.
PLoS ONE
title 4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.
title_full 4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.
title_fullStr 4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.
title_full_unstemmed 4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.
title_short 4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus.
title_sort 4 hydroxy 2 nonenal causes nuclear accumulation of p62 by inhibiting xpo1 and promoting the proteolytic pathway in the nucleus
url https://doi.org/10.1371/journal.pone.0316558
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