Ethnic Variation and Structure-Function Analysis of Tauopathy-Associated <i>PERK</i> Alleles
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Goonho | - |
dc.contributor.author | Galdamez, Angela | - |
dc.contributor.author | Song, Keon-Hyoung | - |
dc.contributor.author | Le, Masako | - |
dc.contributor.author | Kim, Kyle | - |
dc.contributor.author | Lin, Jonathan H. | - |
dc.date.accessioned | 2024-06-12T02:30:51Z | - |
dc.date.available | 2024-06-12T02:30:51Z | - |
dc.date.issued | 2024-05 | - |
dc.identifier.issn | 0021-2148 | - |
dc.identifier.issn | 1869-5868 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/26412 | - |
dc.description.abstract | EIF2AK3, also known as PERK, plays a pivotal role in cellular proteostasis, orchestrating the Unfolded Protein Response (UPR) and Integrated Stress Response (ISR) pathways. In addition to its central position in intracellular stress regulation, human GWAS identify EIF2AK3 as a risk factor in tauopathies, neurodegenerative diseases caused by aberrant tau protein accumulation. Guided by these genomic indicators, our investigation systematically analyzed human PERK variants, focusing on those with potential tauopathy linkages. We assembled a comprehensive data set of human PERK variants associated with Wolcott Rallison Syndrome (WRS), tauopathies, and bioinformatically predicted loss-of-function, referencing the gnomAD, Ensembl, and NCBI databases. We found extensive racial/ethnic variation in the prevalence of common PERK polymorphisms linked to tauopathies. Using SWISS-MODEL, we identified structural perturbations in the ER stress-sensing luminal domain dimers/oligomers of tauopathy-associated PERK variants, Haplotypes A and B, in combination with another tauopathy-linked R240H mutation. Recombinant expression of disease-associated variants in vitro revealed altered PERK signal transduction kinetics in response to ER stress compared to the predominant non-disease variant. In summary, our data further substantiates that human PERK variants identified in tauopathy genetic studies negatively impact PERK structure, function, and downstream signaling with significant variations in prevalence among different racial and ethnic groups. image | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | WILEY-V C H VERLAG GMBH | - |
dc.title | Ethnic Variation and Structure-Function Analysis of Tauopathy-Associated <i>PERK</i> Alleles | - |
dc.type | Article | - |
dc.publisher.location | 독일 | - |
dc.identifier.doi | 10.1002/ijch.202300173 | - |
dc.identifier.scopusid | 2-s2.0-85193949757 | - |
dc.identifier.wosid | 001230310000001 | - |
dc.identifier.bibliographicCitation | ISRAEL JOURNAL OF CHEMISTRY | - |
dc.citation.title | ISRAEL JOURNAL OF CHEMISTRY | - |
dc.type.docType | Article; Early Access | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | PROGRESSIVE SUPRANUCLEAR PALSY | - |
dc.subject.keywordPlus | GENOME-WIDE ASSOCIATION | - |
dc.subject.keywordAuthor | tauopathy | - |
dc.subject.keywordAuthor | ER stress | - |
dc.subject.keywordAuthor | EIF2AK3 | - |
dc.subject.keywordAuthor | PERK Haplotype B | - |
dc.subject.keywordAuthor | PERK R240H variant | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG 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.