Cited 28 times in
KR-POK interacts with p53 and represses its ability to activate transcription of p21WAF1/CDKN1A
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 최원일 | - |
dc.contributor.author | 허만욱 | - |
dc.contributor.author | 고동인 | - |
dc.contributor.author | 김경섭 | - |
dc.contributor.author | 김민경 | - |
dc.contributor.author | 윤채옥 | - |
dc.contributor.author | 전부남 | - |
dc.date.accessioned | 2014-12-19T16:37:11Z | - |
dc.date.available | 2014-12-19T16:37:11Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/89871 | - |
dc.description.abstract | Transcriptional regulation by p53 is thought to play a role in its ability to suppress tumorigenesis. However, there remain gaps in understanding about how p53 regulates transcription and how disrupting this function may promote cancer. Here we report a role in these processes for the kidney cancer-related gene KR-POK (ZBTB7C), a POZ domain and Krüppel-like zinc finger transcription factor that we found to physically interact with p53. Murine embryonic fibroblasts isolated from genetically deficient mice (Kr-pok(-/-) MEFs) exhibited a proliferative defect relative to wild-type mouse embryonic fibroblasts (MEF). The zinc finger domain of Kr-pok interacted directly with the DNA binding and oligomerization domains of p53. This interaction was essential for Kr-pok to bind the distal promoter region of the CDKN1A gene, an important p53 target gene encoding the cell-cycle regulator p21WAF1, and to inhibit p53-mediated transcriptional activation of CDKN1A. Kr-pok also interacted with the transcriptional corepressors NCoR and BCoR, acting to repress histone H3 and H4 deacetylation at the proximal promoter region of the CDKN1A gene. Importantly, Kr-pok(-/-) MEFs displayed an enhancement in CDKN1A transactivation by p53 during the DNA damage response, without any parallel changes in transcription of either the p53 or Kr-pok genes themselves. Furthermore, Kr-pok promoted cell proliferation in vitro and in vivo, and its expression was increased in more than 50% of the malignant human kidney cancer cases analyzed. Together, our findings define KR-POK as a transcriptional repressor with a pro-oncogenic role that relies upon binding to p53 and inhibition of its transactivation function. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
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 | Animals | - |
dc.subject.MESH | Cell Proliferation | - |
dc.subject.MESH | Cyclin-Dependent Kinase Inhibitor p21/genetics* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Fibroblasts/metabolism | - |
dc.subject.MESH | Gene Knockout Techniques | - |
dc.subject.MESH | Genes, p53* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Kidney Neoplasms/genetics* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | NIH 3T3 Cells | - |
dc.subject.MESH | Promoter Regions, Genetic | - |
dc.subject.MESH | Proteins/genetics* | - |
dc.subject.MESH | Proto-Oncogene Proteins | - |
dc.subject.MESH | Transcription Factors/metabolism | - |
dc.subject.MESH | Transcriptional Activation* | - |
dc.subject.MESH | Zinc Fingers | - |
dc.title | KR-POK interacts with p53 and represses its ability to activate transcription of p21WAF1/CDKN1A | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry & Molecular Biology (생화학,분자생물학) | - |
dc.contributor.googleauthor | Bu-Nam Jeon | - |
dc.contributor.googleauthor | Min-Kyeong Kim | - |
dc.contributor.googleauthor | Won-Il Choi | - |
dc.contributor.googleauthor | Dong-In Koh | - |
dc.contributor.googleauthor | Sung-Yi Hong | - |
dc.contributor.googleauthor | Kyung-Sup Kim | - |
dc.contributor.googleauthor | Minjung Kim | - |
dc.contributor.googleauthor | Chae-Ok Yun | - |
dc.contributor.googleauthor | Juyong Yoon | - |
dc.contributor.googleauthor | Kang-Yell Choi | - |
dc.contributor.googleauthor | Kyung-Ryul Lee | - |
dc.contributor.googleauthor | Kenneth P. Nephew | - |
dc.contributor.googleauthor | Man-Wook Hur | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-11-2433 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A04126 | - |
dc.contributor.localId | A04350 | - |
dc.contributor.localId | A00114 | - |
dc.contributor.localId | A00297 | - |
dc.contributor.localId | A00456 | - |
dc.contributor.localId | A02614 | - |
dc.contributor.localId | A03517 | - |
dc.relation.journalcode | J00452 | - |
dc.identifier.eissn | 1538-7445 | - |
dc.identifier.pmid | 22253232 | - |
dc.contributor.alternativeName | Choi, Won Il | - |
dc.contributor.alternativeName | Hur, Man Wook | - |
dc.contributor.alternativeName | Koh, Dong In | - |
dc.contributor.alternativeName | Kim, Kyung Sup | - |
dc.contributor.alternativeName | Kim, Min Kyeong | - |
dc.contributor.alternativeName | Yun, Chae Ok | - |
dc.contributor.alternativeName | Jeon, Bu Nam | - |
dc.contributor.affiliatedAuthor | Choi, Won Il | - |
dc.contributor.affiliatedAuthor | Hur, Man Wook | - |
dc.contributor.affiliatedAuthor | Koh, Dong In | - |
dc.contributor.affiliatedAuthor | Kim, Kyung Sup | - |
dc.contributor.affiliatedAuthor | Kim, Min Kyeong | - |
dc.contributor.affiliatedAuthor | Yun, Chae Ok | - |
dc.contributor.affiliatedAuthor | Jeon, Bu Nam | - |
dc.citation.volume | 72 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1137 | - |
dc.citation.endPage | 1148 | - |
dc.identifier.bibliographicCitation | CANCER RESEARCH, Vol.72(5) : 1137-1148, 2012 | - |
dc.identifier.rimsid | 31955 | - |
dc.type.rims | ART | - |
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