Cited 18 times in
Destabilization and Mislocalization of POU3F4 by C-Terminal Frameshift Truncation and Extension Mutation
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 복진웅 | - |
dc.date.accessioned | 2014-12-18T09:03:58Z | - |
dc.date.available | 2014-12-18T09:03:58Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 1059-7794 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/87468 | - |
dc.description.abstract | Most X-linked nonsyndromic hearing loss is caused by various types of mutations of the POU domain class 3 transcription factor 4 gene (POU3F4). We found five unique missense and frameshift truncation and extension mutations in Korean patients. Two missense mutations (p.Thr211Met and p.Gln229Arg) disturbed transcriptional activity. Two frameshift extension mutations (p.Thr354GlnfsX115 and p.X362ArgextX113) were located outside of POU domain and nuclear localization signal (NLS) at the C-terminus. POU3F4 protein levels were low and could be restored by MG132, a proteasome inhibitor, in vitro. These mutant POU3F4 proteins were exclusively localized to the cytoplasm and did not have transcriptional activity. Frameshift mutation (p.Leu317PhefsX12) in POU3F4 leads to the truncation of the C-terminal 44 amino acids spanning the POU domain and NLS. This frameshift truncation mutant protein was located in both the nucleus and cytoplasm and was present at low protein levels. This mutant was also transcriptionally inactive, even in the presence of MG132. From these results, we conclude that frameshift truncation and extension mutations in the C-terminus of POU3F4 lead to cytoplasmic localization and subsequent proteosomal degradation due to structural aberrations, which cause transcriptional inactivity and thus nonsyndromic hearing loss. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | HUMAN MUTATION | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adolescent | - |
dc.subject.MESH | Amino Acid Sequence | - |
dc.subject.MESH | Asian Continental Ancestry Group/genetics | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Child | - |
dc.subject.MESH | Child, Preschool | - |
dc.subject.MESH | Fluorescent Antibody Technique | - |
dc.subject.MESH | Frameshift Mutation* | - |
dc.subject.MESH | Gene Frequency | - |
dc.subject.MESH | HEK293 Cells | - |
dc.subject.MESH | Hearing Loss, Sensorineural/genetics* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Leupeptins/pharmacology | - |
dc.subject.MESH | Magnetic Resonance Imaging | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Molecular Sequence Data | - |
dc.subject.MESH | Mutation, Missense | - |
dc.subject.MESH | Nuclear Localization Signals | - |
dc.subject.MESH | POU Domain Factors/genetics* | - |
dc.subject.MESH | POU Domain Factors/metabolism | - |
dc.subject.MESH | Pedigree | - |
dc.subject.MESH | Phenotype | - |
dc.subject.MESH | Proteasome Inhibitors/pharmacology | - |
dc.subject.MESH | Protein Conformation | - |
dc.subject.MESH | Transcriptional Activation/genetics | - |
dc.title | Destabilization and Mislocalization of POU3F4 by C-Terminal Frameshift Truncation and Extension Mutation | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Anatomy (해부학) | - |
dc.contributor.googleauthor | Byung Yoon Choi | - |
dc.contributor.googleauthor | Do-Hwan Kim | - |
dc.contributor.googleauthor | Taesu Chung | - |
dc.contributor.googleauthor | Mi Chang | - |
dc.contributor.googleauthor | Eun-Hye Kim | - |
dc.contributor.googleauthor | Ah Reum Kim | - |
dc.contributor.googleauthor | Jungirl Seok | - |
dc.contributor.googleauthor | Sun O Chang | - |
dc.contributor.googleauthor | Jinwoong Bok | - |
dc.contributor.googleauthor | Dongsup Kim | - |
dc.contributor.googleauthor | Seung-Ha Oh | - |
dc.contributor.googleauthor | Woong-Yang Park | - |
dc.identifier.doi | 10.1002/humu.22232 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01865 | - |
dc.relation.journalcode | J01010 | - |
dc.identifier.eissn | 1098-1004 | - |
dc.identifier.pmid | 23076972 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1002/humu.22232/abstract | - |
dc.subject.keyword | Adolescent | - |
dc.subject.keyword | Amino Acid Sequence | - |
dc.subject.keyword | Asian Continental Ancestry Group/genetics | - |
dc.subject.keyword | Blotting, Western | - |
dc.subject.keyword | Child | - |
dc.subject.keyword | Child, Preschool | - |
dc.subject.keyword | Fluorescent Antibody Technique | - |
dc.subject.keyword | Frameshift Mutation* | - |
dc.subject.keyword | Gene Frequency | - |
dc.subject.keyword | HEK293 Cells | - |
dc.subject.keyword | Hearing Loss, Sensorineural/genetics* | - |
dc.subject.keyword | Humans | - |
dc.subject.keyword | Leupeptins/pharmacology | - |
dc.subject.keyword | Magnetic Resonance Imaging | - |
dc.subject.keyword | Male | - |
dc.subject.keyword | Molecular Sequence Data | - |
dc.subject.keyword | Mutation, Missense | - |
dc.subject.keyword | Nuclear Localization Signals | - |
dc.subject.keyword | POU Domain Factors/genetics* | - |
dc.subject.keyword | POU Domain Factors/metabolism | - |
dc.subject.keyword | Pedigree | - |
dc.subject.keyword | Phenotype | - |
dc.subject.keyword | Proteasome Inhibitors/pharmacology | - |
dc.subject.keyword | Protein Conformation | - |
dc.subject.keyword | Transcriptional Activation/genetics | - |
dc.contributor.alternativeName | Bok, Jin Woong | - |
dc.contributor.affiliatedAuthor | Bok, Jin Woong | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 34 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 309 | - |
dc.citation.endPage | 316 | - |
dc.identifier.bibliographicCitation | HUMAN MUTATION, Vol.34(2) : 309-316, 2013 | - |
dc.identifier.rimsid | 34246 | - |
dc.type.rims | ART | - |
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