The E2 ubiquitin-conjugating enzyme HIP2 is a crucial regulator of quality control against mutant SOD1 proteotoxicity
DC Field | Value | Language |
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dc.contributor.author | Tak, Yeong Jin | - |
dc.contributor.author | Kang, Seongman | - |
dc.date.accessioned | 2022-04-01T16:41:12Z | - |
dc.date.available | 2022-04-01T16:41:12Z | - |
dc.date.created | 2022-04-01 | - |
dc.date.issued | 2022-02-01 | - |
dc.identifier.issn | 0925-4439 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/139383 | - |
dc.description.abstract | Mutations in superoxide dismutase 1 (SOD1) leading to the formation of intracellular protein aggregates cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder characterized by a selective degeneration of motor neurons. The ALS-linked mutant SOD1 emerged as a possible target for ubiquitin-proteasome system (UPS)-mediated degradation. We aimed to elucidate the role of huntingtin interaction protein 2 (HIP2), an E2 ubiquitin-conjugating enzyme, in the proteotoxicity of mutant SOD1 aggregates. We found that HIP2 interacts with mutant SOD1, but not wild-type SOD1, and is upregulated in response to mutant SOD1 expression. Upregulation of HIP2 protein was observed in the spinal cord of 16-week-old SOD1-G93A transgenic mice. HIP2 further modified mutant SOD1 proteins via K48-linked polyubiquitination and degraded mutant SOD1 proteins through the UPS. Upregulation of HIP2 protected cells from mutant SOD1-induced toxicity. Taken together, our findings demonstrate that HIP2 is a crucial regulator of quality control against the proteotoxicity of mutant SOD1. Our results suggest that modulating HIP2 may represent a novel therapeutic strategy for the treatment of ALS. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.subject | MOTOR-NEURON DEATH | - |
dc.subject | SUPEROXIDE-DISMUTASE | - |
dc.subject | PROTEASOME SYSTEM | - |
dc.subject | ALS | - |
dc.subject | E2-25K | - |
dc.subject | PROTEOSTASIS | - |
dc.title | The E2 ubiquitin-conjugating enzyme HIP2 is a crucial regulator of quality control against mutant SOD1 proteotoxicity | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kang, Seongman | - |
dc.identifier.doi | 10.1016/j.bbadis.2021.166316 | - |
dc.identifier.scopusid | 2-s2.0-85120425055 | - |
dc.identifier.wosid | 000728993500002 | - |
dc.identifier.bibliographicCitation | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v.1868, no.2 | - |
dc.relation.isPartOf | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | - |
dc.citation.title | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | - |
dc.citation.volume | 1868 | - |
dc.citation.number | 2 | - |
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 | Biophysics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | MOTOR-NEURON DEATH | - |
dc.subject.keywordPlus | SUPEROXIDE-DISMUTASE | - |
dc.subject.keywordPlus | PROTEASOME SYSTEM | - |
dc.subject.keywordPlus | ALS | - |
dc.subject.keywordPlus | E2-25K | - |
dc.subject.keywordPlus | PROTEOSTASIS | - |
dc.subject.keywordAuthor | ALS | - |
dc.subject.keywordAuthor | SOD1 | - |
dc.subject.keywordAuthor | Protein aggregates | - |
dc.subject.keywordAuthor | HIP2 | - |
dc.subject.keywordAuthor | UPS | - |
dc.subject.keywordAuthor | Proteotoxicity | - |
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