E3 Ubiquitin Ligase APC/C-Cdh1 Regulation of Phenylalanine Hydroxylase Stability and Function
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Tyagi, Apoorvi | - |
dc.contributor.author | Sarodaya, Neha | - |
dc.contributor.author | Kaushal, Kamini | - |
dc.contributor.author | Chandrasekaran, Arun Pandian | - |
dc.contributor.author | Antao, Ainsley Mike | - |
dc.contributor.author | Suresh, Bharathi | - |
dc.contributor.author | Rhie, Byung Ho | - |
dc.contributor.author | Kim, Kye Seong | - |
dc.contributor.author | Ramakrishna, Suresh | - |
dc.date.accessioned | 2022-07-07T09:33:18Z | - |
dc.date.available | 2022-07-07T09:33:18Z | - |
dc.date.issued | 2020-12 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/144280 | - |
dc.description.abstract | Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by the dysfunction of the enzyme phenylalanine hydroxylase (PAH). Alterations in the level of PAH leads to the toxic accumulation of phenylalanine in the blood and brain. Protein degradation mediated by ubiquitination is a principal cellular process for maintaining protein homeostasis. Therefore, it is important to identify the E3 ligases responsible for PAH turnover and proteostasis. Here, we report that anaphase-promoting complex/cyclosome-Cdh1 (APC/C)(Cdh1) is an E3 ubiquitin ligase complex that interacts and promotes the polyubiquitination of PAH through the 26S proteasomal pathway. Cdh1 destabilizes and declines the half-life of PAH. In contrast, the CRISPR/Cas9-mediated knockout of Cdh1 stabilizes PAH expression and enhances phenylalanine metabolism. Additionally, our current study demonstrates the clinical relevance of PAH and Cdh1 correlation in hepatocellular carcinoma (HCC). Overall, we show that PAH is a prognostic marker for HCC and Cdh1 could be a potential therapeutic target to regulate PAH-mediated physiological and metabolic disorders. | - |
dc.format.extent | 19 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | MDPI | - |
dc.title | E3 Ubiquitin Ligase APC/C-Cdh1 Regulation of Phenylalanine Hydroxylase Stability and Function | - |
dc.type | Article | - |
dc.publisher.location | 스위스 | - |
dc.identifier.doi | 10.3390/ijms21239076 | - |
dc.identifier.scopusid | 2-s2.0-85096840093 | - |
dc.identifier.wosid | 000597930800001 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.23, pp 1 - 19 | - |
dc.citation.title | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.citation.volume | 21 | - |
dc.citation.number | 23 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 19 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | anaphase promoting complex | - |
dc.subject.keywordPlus | phenylalanine | - |
dc.subject.keywordPlus | phenylalanine 4 monooxygenase | - |
dc.subject.keywordPlus | proteasome | - |
dc.subject.keywordPlus | ubiquitin protein ligase E3 | - |
dc.subject.keywordPlus | uvomorulin | - |
dc.subject.keywordPlus | anaphase promoting complex | - |
dc.subject.keywordPlus | ATP dependent 26S protease | - |
dc.subject.keywordPlus | phenylalanine | - |
dc.subject.keywordPlus | phenylalanine 4 monooxygenase | - |
dc.subject.keywordPlus | polyubiquitin | - |
dc.subject.keywordPlus | proteasome | - |
dc.subject.keywordPlus | protein binding | - |
dc.subject.keywordPlus | ubiquitin protein ligase | - |
dc.subject.keywordPlus | amino acid metabolism | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | cancer patient | - |
dc.subject.keywordPlus | cancer prognosis | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | CRISPR-CAS9 system | - |
dc.subject.keywordPlus | embryo | - |
dc.subject.keywordPlus | enzyme activity | - |
dc.subject.keywordPlus | enzyme stability | - |
dc.subject.keywordPlus | gene knockout | - |
dc.subject.keywordPlus | half life time | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | human tissue | - |
dc.subject.keywordPlus | protein expression | - |
dc.subject.keywordPlus | protein protein interaction | - |
dc.subject.keywordPlus | signal transduction | - |
dc.subject.keywordPlus | turnover rate | - |
dc.subject.keywordPlus | ubiquitination | - |
dc.subject.keywordPlus | enzyme stability | - |
dc.subject.keywordPlus | HEK293 cell line | - |
dc.subject.keywordPlus | liver cell carcinoma | - |
dc.subject.keywordPlus | liver tumor | - |
dc.subject.keywordPlus | metabolism | - |
dc.subject.keywordPlus | pathology | - |
dc.subject.keywordPlus | protein degradation | - |
dc.subject.keywordPlus | ubiquitination | - |
dc.subject.keywordAuthor | enzyme assay | - |
dc.subject.keywordAuthor | hyperphenylalaninemia | - |
dc.subject.keywordAuthor | liver cancer | - |
dc.subject.keywordAuthor | neurological damage | - |
dc.subject.keywordAuthor | tetrahydrobiopterin | - |
dc.subject.keywordAuthor | ubiquitin-proteasome system | - |
dc.identifier.url | https://www.mdpi.com/1422-0067/21/23/9076 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
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.