432 778

Cited 13 times in

ABCD2 Is a Direct Target of β-Catenin and TCF-4: Implications for X-Linked Adrenoleukodystrophy Therapy

DC Field Value Language
dc.contributor.author김동욱-
dc.contributor.author김한수-
dc.contributor.author박철용-
dc.contributor.author유정은-
dc.contributor.author이동진-
dc.contributor.author이재석-
dc.contributor.author이현지-
dc.contributor.author장지호-
dc.date.accessioned2014-12-18T09:26:07Z-
dc.date.available2014-12-18T09:26:07Z-
dc.date.issued2013-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/88164-
dc.description.abstractX-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene that encodes the peroxisomal ATP-binding cassette (ABC) transporter subfamily D member 1 protein (ABCD1), which is referred to as the adrenoleukodystrophy protein (ALDP). Induction of the ABCD2 gene, the closest homolog of ABCD1, has been mentioned as a possible therapeutic option for the defective ABCD1 protein in X-ALD. However, little is known about the transcriptional regulation of ABCD2 gene expression. Here, through in silico analysis, we found two putative TCF-4 binding elements between nucleotide positions −360 and −260 of the promoter region of the ABCD2 gene. The transcriptional activity of the ABCD2 promoter was strongly increased by ectopic expression of β-catenin and TCF-4. In addition, mutation of either or both TCF-4 binding elements by site-directed mutagenesis decreased promoter activity. This was further validated by the finding that β-catenin and the promoter of the ABCD2 gene were pulled down with a β-catenin antibody in a chromatin immunoprecipitation assay. Moreover, real-time PCR analysis revealed that β-catenin and TCF-4 increased mRNA levels of ABCD2 in both a hepatocellular carcinoma cell line and primary fibroblasts from an X-ALD patient. Interestingly, we found that the levels of very long chain fatty acids were decreased by ectopic expression of ABCD2-GFP as well as β-catenin and TCF-4. Taken together, our results demonstrate for the first time the direct regulation of ABCD2 by β-catenin and TCF-4.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHATP Binding Cassette Transporter, Sub-Family D-
dc.subject.MESHATP-Binding Cassette Transporters/genetics*-
dc.subject.MESHAdrenoleukodystrophy/genetics*-
dc.subject.MESHAdrenoleukodystrophy/pathology-
dc.subject.MESHAdrenoleukodystrophy/therapy*-
dc.subject.MESHBase Sequence-
dc.subject.MESHBasic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism*-
dc.subject.MESHBinding Sites/genetics-
dc.subject.MESHFatty Acids/metabolism-
dc.subject.MESHFibroblasts/metabolism-
dc.subject.MESHFibroblasts/pathology-
dc.subject.MESHGene Silencing-
dc.subject.MESHGreen Fluorescent Proteins/metabolism-
dc.subject.MESHHep G2 Cells-
dc.subject.MESHHumans-
dc.subject.MESHMolecular Sequence Data-
dc.subject.MESHMolecular Targeted Therapy*-
dc.subject.MESHPromoter Regions, Genetic/genetics-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHRecombinant Fusion Proteins/metabolism-
dc.subject.MESHTranscription Factor 4-
dc.subject.MESHTranscription Factors/metabolism*-
dc.subject.MESHTranscription, Genetic-
dc.subject.MESHTranscriptional Activation/genetics-
dc.subject.MESHUp-Regulation/genetics-
dc.subject.MESHbeta Catenin/metabolism*-
dc.titleABCD2 Is a Direct Target of β-Catenin and TCF-4: Implications for X-Linked Adrenoleukodystrophy Therapy-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Laboratory Medicine (진단검사의학)-
dc.contributor.googleauthorChul-Yong Park-
dc.contributor.googleauthorHan-Soo Kim-
dc.contributor.googleauthorJiho Jang-
dc.contributor.googleauthorHyunji Lee-
dc.contributor.googleauthorJae Souk Lee-
dc.contributor.googleauthorJeong-Eun Yoo-
dc.contributor.googleauthorDongjin R. Lee-
dc.contributor.googleauthorDong-Wook Kim-
dc.identifier.doi10.1371/journal.pone.0056242-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01100-
dc.contributor.localIdA01719-
dc.contributor.localIdA02734-
dc.contributor.localIdA03074-
dc.contributor.localIdA03299-
dc.contributor.localIdA03480-
dc.contributor.localIdA02505-
dc.contributor.localIdA00406-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid23437103-
dc.subject.keywordATP Binding Cassette Transporter, Sub-Family D-
dc.subject.keywordATP-Binding Cassette Transporters/genetics*-
dc.subject.keywordAdrenoleukodystrophy/genetics*-
dc.subject.keywordAdrenoleukodystrophy/pathology-
dc.subject.keywordAdrenoleukodystrophy/therapy*-
dc.subject.keywordBase Sequence-
dc.subject.keywordBasic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism*-
dc.subject.keywordBinding Sites/genetics-
dc.subject.keywordFatty Acids/metabolism-
dc.subject.keywordFibroblasts/metabolism-
dc.subject.keywordFibroblasts/pathology-
dc.subject.keywordGene Silencing-
dc.subject.keywordGreen Fluorescent Proteins/metabolism-
dc.subject.keywordHep G2 Cells-
dc.subject.keywordHumans-
dc.subject.keywordMolecular Sequence Data-
dc.subject.keywordMolecular Targeted Therapy*-
dc.subject.keywordPromoter Regions, Genetic/genetics-
dc.subject.keywordRNA, Messenger/genetics-
dc.subject.keywordRNA, Messenger/metabolism-
dc.subject.keywordRecombinant Fusion Proteins/metabolism-
dc.subject.keywordTranscription Factor 4-
dc.subject.keywordTranscription Factors/metabolism*-
dc.subject.keywordTranscription, Genetic-
dc.subject.keywordTranscriptional Activation/genetics-
dc.subject.keywordUp-Regulation/genetics-
dc.subject.keywordbeta Catenin/metabolism*-
dc.contributor.alternativeNameKim, Dong Wook-
dc.contributor.alternativeNameKim, Han Soo-
dc.contributor.alternativeNamePark, Chul Yong-
dc.contributor.alternativeNameYoo, Jeong Eun-
dc.contributor.alternativeNameLee, Dongjin R.-
dc.contributor.alternativeNameLee, Jae Souk-
dc.contributor.alternativeNameLee, Hyun Ji-
dc.contributor.alternativeNameJang, Ji Ho-
dc.contributor.affiliatedAuthorKim, Han Soo-
dc.contributor.affiliatedAuthorPark, Chul Yong-
dc.contributor.affiliatedAuthorLee, Dongjin R.-
dc.contributor.affiliatedAuthorLee, Jae Souk-
dc.contributor.affiliatedAuthorLee, Hyun Ji-
dc.contributor.affiliatedAuthorJang, Ji Ho-
dc.contributor.affiliatedAuthorYoo, Jeong Eun-
dc.contributor.affiliatedAuthorKim, Dong Wook-
dc.rights.accessRightsfree-
dc.citation.volume8-
dc.citation.number2-
dc.citation.startPagee56242-
dc.identifier.bibliographicCitationPLOS ONE, Vol.8(2) : e56242, 2013-
dc.identifier.rimsid33101-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.