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The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding

DC FieldValueLanguage
dc.contributor.author고동인-
dc.contributor.author윤재현-
dc.contributor.author전부남-
dc.contributor.author최원일-
dc.contributor.author허만욱-
dc.date.accessioned2014-12-19T17:31:51Z-
dc.date.available2014-12-19T17:31:51Z-
dc.date.issued2012-
dc.identifier.issn0950-9232-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/91581-
dc.description.abstractThe BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box#3 (bp, -55 to -63) and the MIZ-1-binding elements, MRE-A (bp, -90 to -64) and MRE-B (bp, -27 to -17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp, -95 to -100) and #3 (bp, -55 to -63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfOncogene-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleThe proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Biochemistry & Molecular Biology (생화학,분자생물학)-
dc.contributor.googleauthorK M Lee-
dc.contributor.googleauthorW I Choi-
dc.contributor.googleauthorD I Koh-
dc.contributor.googleauthorY J Kim-
dc.contributor.googleauthorB N Jeon-
dc.contributor.googleauthorJ H Yoon-
dc.contributor.googleauthorC E Lee-
dc.contributor.googleauthorS H Kim-
dc.contributor.googleauthorJ Oh-
dc.contributor.googleauthorM W Hur-
dc.identifier.doi10.1038/onc.2011.331-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00114-
dc.contributor.localIdA02592-
dc.contributor.localIdA03517-
dc.contributor.localIdA04126-
dc.contributor.localIdA04350-
dc.relation.journalcodeJ02413-
dc.identifier.urlhttp://www.nature.com/onc/journal/v31/n11/full/onc2011331a.html-
dc.contributor.alternativeNameKoh, Dong In-
dc.contributor.alternativeNameYoon, Jae Hyeon-
dc.contributor.alternativeNameJeon, Bu Nam-
dc.contributor.alternativeNameChoi, Won Il-
dc.contributor.alternativeNameHur, Man Wook-
dc.contributor.affiliatedAuthorKoh, Dong In-
dc.contributor.affiliatedAuthorYoon, Jae Hyeon-
dc.contributor.affiliatedAuthorJeon, Bu Nam-
dc.contributor.affiliatedAuthorChoi, Won Il-
dc.contributor.affiliatedAuthorHur, Man Wook-
dc.citation.volume31-
dc.citation.number11-
dc.citation.startPage1442-
dc.citation.endPage1458-
dc.identifier.bibliographicCitationOncogene, Vol.31(11) : 1442-1458, 2012-
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)

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