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Promyelocytic Leukemia Zinc Finger-Retinoic Acid Receptor α (PLZF-RARα), an Oncogenic Transcriptional Repressor of Cyclin-dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) and Tumor Protein p53 (TP53) Genes

DC FieldValueLanguage
dc.contributor.author김건홍-
dc.contributor.author김민영-
dc.contributor.author윤재현-
dc.contributor.author최원일-
dc.contributor.author허만욱-
dc.date.accessioned2015-01-06T16:55:39Z-
dc.date.available2015-01-06T16:55:39Z-
dc.date.issued2014-
dc.identifier.issn0021-9258-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/99039-
dc.description.abstractPromyelocytic leukemia zinc finger-retinoic acid receptor α (PLZF-RARα) is an oncogene transcriptional repressor that is generated by a chromosomal translocation between the PLZF and RARα genes in acute promyelocytic leukemia (APL-type) patients. The molecular interaction between PLZF-RARα and the histone deacetylase corepressor was proposed to be important in leukemogenesis. We found that PLZF-RARα can repress transcription of the p21WAF/CDKN1A gene, which encodes the negative cell cycle regulator p21 by binding to its proximal promoter Sp1-binding GC-boxes 3, 4, 5/6, a retinoic acid response element (RARE), and distal p53-responsive elements (p53REs). PLZF-RARα also acts as a competitive transcriptional repressor of p53, RARα, and Sp1. PLZF-RARα interacts with co-repressors such as mSin3A, NCoR, and SMRT, thereby deacetylating histones Ac-H3 and Ac-H4 at the CDKN1A promoter. PLZF-RARα also interacts with the MBD3-NuRD complex, leading to epigenetic silencing of CDKN1A through DNA methylation. Furthermore, PLZF-RARα represses TP53 and increases p53 protein degradation by ubiquitination, further repressing p21 expression. Resultantly, PLZF-RARα promotes cell proliferation and significantly increases the number of cells in S-phase.-
dc.description.statementOfResponsibilityopen-
dc.format.extent18641~18656-
dc.relation.isPartOfJOURNAL OF BIOLOGICAL CHEMISTRY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHBinding, Competitive-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCyclin-Dependent Kinase Inhibitor p21/deficiency-
dc.subject.MESHCyclin-Dependent Kinase Inhibitor p21/genetics*-
dc.subject.MESHDNA (Cytosine-5-)-Methyltransferases/metabolism-
dc.subject.MESHDNA Methylation-
dc.subject.MESHDNA-Binding Proteins/metabolism-
dc.subject.MESHEpigenesis, Genetic-
dc.subject.MESHGene Silencing-
dc.subject.MESHHistone Deacetylases/metabolism-
dc.subject.MESHHistones/metabolism-
dc.subject.MESHHumans-
dc.subject.MESHMi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism-
dc.subject.MESHOncogene Proteins, Fusion/metabolism*-
dc.subject.MESHPromoter Regions, Genetic/genetics-
dc.subject.MESHProtein Stability-
dc.subject.MESHRepressor Proteins/metabolism*-
dc.subject.MESHS Phase-
dc.subject.MESHSp1 Transcription Factor/metabolism-
dc.subject.MESHTranscription, Genetic/genetics*-
dc.subject.MESHTumor Suppressor Protein p53/genetics*-
dc.titlePromyelocytic Leukemia Zinc Finger-Retinoic Acid Receptor α (PLZF-RARα), an Oncogenic Transcriptional Repressor of Cyclin-dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) and Tumor Protein p53 (TP53) Genes-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Life Science (의생명과학부)-
dc.contributor.googleauthorWon-Il Choi-
dc.contributor.googleauthorJae-Hyeon Yoon-
dc.contributor.googleauthorMin-Young Kim-
dc.contributor.googleauthorDong-In Koh-
dc.contributor.googleauthorJonathan D. Licht-
dc.contributor.googleauthorKunhong Kim-
dc.contributor.googleauthorMan-Wook Hur-
dc.identifier.doi10.1074/jbc.M113.538777-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00289-
dc.contributor.localIdA02592-
dc.contributor.localIdA04126-
dc.contributor.localIdA04350-
dc.contributor.localIdA00467-
dc.relation.journalcodeJ01258-
dc.identifier.eissn1083-351X-
dc.identifier.pmid24821728-
dc.identifier.urlhttp://www.jbc.org/content/289/27/18641.long-
dc.subject.keywordLeukemia-
dc.subject.keywordOncogene-
dc.subject.keywordPLZF-RAR-
dc.subject.keywordTranscription Regulation-
dc.subject.keywordTranscription Repressor-
dc.subject.keywordp21WAF/CDKN1A-
dc.subject.keywordp53-
dc.contributor.alternativeNameKim, Kun Hong-
dc.contributor.alternativeNameKim, Min Young-
dc.contributor.alternativeNameYoon, Jae Hyeon-
dc.contributor.alternativeNameChoi, Won Il-
dc.contributor.alternativeNameHur, Man Wook-
dc.contributor.affiliatedAuthorKim, Kun Hong-
dc.contributor.affiliatedAuthorYoon, Jae Hyeon-
dc.contributor.affiliatedAuthorChoi, Won Il-
dc.contributor.affiliatedAuthorHur, Man Wook-
dc.contributor.affiliatedAuthorKim, Min Young-
dc.rights.accessRightsfree-
dc.citation.volume289-
dc.citation.number27-
dc.citation.startPage18641-
dc.citation.endPage18656-
dc.identifier.bibliographicCitationJOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(27) : 18641-18656, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

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