Amyotrophic lateral sclerosis-related mutant superoxide dismutase 1 aggregates inhibit 14-3-3-mediated cell survival by sequestration into the JUNQ compartment
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Ju-Hwang | - |
dc.contributor.author | Jang, Hae Rim | - |
dc.contributor.author | Lee, In Young | - |
dc.contributor.author | Oh, Hye Kyung | - |
dc.contributor.author | Choi, Eui-Ju | - |
dc.contributor.author | Rhim, Hyangshuk | - |
dc.contributor.author | Kang, Seongman | - |
dc.date.accessioned | 2021-09-03T01:46:32Z | - |
dc.date.available | 2021-09-03T01:46:32Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2017-09-15 | - |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/82232 | - |
dc.description.abstract | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss in the spinal cord and brain. Mutations in the superoxide dismutase 1 (SOD1) gene have been linked to familial ALS. To elucidate the role of SOD1 mutations in ALS, we investigated 14-3-3, a crucial regulator of cell death that was identified in patients with familial ALS. In a transgenic mouse model (SOD1-G93A) of ALS, 14-3-3 co-localized with mutant SOD1 aggregates and was more insoluble in the spinal cords of mutant SOD1 transgenic mice than in those of wild-type mice. Immunofluorescence and co-immunoprecipitation experiments showed that the 14-3-3 epsilon and 0 isoforms interact with mutant SOD1 aggregates in the juxtanuclear quality control compartment of N2a neuroblastoma cells. Fluorescence loss in photobleaching experiments revealed that movement of the isoforms of 14-3-3 was markedly reduced in SOD1 aggregates. Bax translocation into and cytochrome c release from the mitochondria were promoted by the sequestration of 14-3-3 into mutant SOD1 aggregates, increasing cell death. Mutant SOD1 aggregates were dissolved by the Hsp104 chaperone, which increased the interaction of 14-3-3 with Bax, reducing cell death. Our study demonstrates that mutant SOD1 inhibits 14-3-3-mediated cell survival. This information may contribute to the identification of a novel therapeutic target for ALS. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.subject | MOTOR-NEURON DISEASE | - |
dc.subject | LINKED SOD1 MUTANTS | - |
dc.subject | MOUSE MODEL | - |
dc.subject | PROTEIN AGGREGATION | - |
dc.subject | FAMILIAL ALS | - |
dc.subject | AXONAL-TRANSPORT | - |
dc.subject | MISFOLDED PROTEINS | - |
dc.subject | TRANSGENIC MICE | - |
dc.subject | QUALITY-CONTROL | - |
dc.subject | ER STRESS | - |
dc.title | Amyotrophic lateral sclerosis-related mutant superoxide dismutase 1 aggregates inhibit 14-3-3-mediated cell survival by sequestration into the JUNQ compartment | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Eui-Ju | - |
dc.contributor.affiliatedAuthor | Kang, Seongman | - |
dc.identifier.doi | 10.1093/hmg/ddx250 | - |
dc.identifier.scopusid | 2-s2.0-85029662950 | - |
dc.identifier.wosid | 000409091200014 | - |
dc.identifier.bibliographicCitation | HUMAN MOLECULAR GENETICS, v.26, no.18, pp.3615 - 3629 | - |
dc.relation.isPartOf | HUMAN MOLECULAR GENETICS | - |
dc.citation.title | HUMAN MOLECULAR GENETICS | - |
dc.citation.volume | 26 | - |
dc.citation.number | 18 | - |
dc.citation.startPage | 3615 | - |
dc.citation.endPage | 3629 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | MOTOR-NEURON DISEASE | - |
dc.subject.keywordPlus | LINKED SOD1 MUTANTS | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | PROTEIN AGGREGATION | - |
dc.subject.keywordPlus | FAMILIAL ALS | - |
dc.subject.keywordPlus | AXONAL-TRANSPORT | - |
dc.subject.keywordPlus | MISFOLDED PROTEINS | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | QUALITY-CONTROL | - |
dc.subject.keywordPlus | ER STRESS | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.