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A novel POK family transcription factor, ZBTB5, represses transcription of p21CIP1 gene.

Authors
 Dong-In Koh  ;  Won-Il Choi  ;  Bu-Nam Jeon  ;  Choong-Eun Lee  ;  Chae-Ok Yun  ;  Man-Wook Hur 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.284(30) : 19856-19866, 2009 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2009
MeSH
Animals ; Binding Sites ; Cell Cycle ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Cercopithecus aethiops ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Gene Expression Regulation* ; Histone Deacetylases/metabolism ; Humans ; Kidney/cytology ; Kruppel-Like Transcription Factors/analysis* ; Kruppel-Like Transcription Factors/chemistry ; Kruppel-Like Transcription Factors/genetics* ; Kruppel-Like Transcription Factors/metabolism ; Mice ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-mdm2/genetics ; Retinal Neoplasms/genetics ; Retinoblastoma/genetics ; Sp1 Transcription Factor/genetics ; Sp1 Transcription Factor/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Zinc Fingers
Abstract
Transcriptional repression through chromatin remodeling and histone deacetylation has been postulated as a driving force for tumorigenesis. We isolated and characterized a novel POZ domain Krüppel-like zinc finger transcription repressor, ZBTB5 (zinc finger and BTB domain-containing 5). Serial analysis of gene expression (SAGE) analysis showed that ZBTB5 expression is higher in retinoblastoma and muscle cancer tissues. Immunocytochemistry showed that ZBTB5 was localized to the nucleus, particularly nuclear speckles. ZBTB5 directly repressed transcription of cell cycle arrest gene p21 by binding to the proximal GC-box 5/6 elements and the two distal p53-responsive elements (bp -2323 approximately -2299; bp -1416 approximately -1392). Chromatin immunoprecipitation assays showed that ZBTB5 and p53 competed with each other in occupying the p53 binding elements. ZBTB5 interacted with co-repressor-histone deacetylase complexes such as BCoR (BCL-6-interacting corepressor), NCoR (nuclear receptor corepressor), and SMRT (silencing mediator for retinoid and thyroid receptors) via its POZ domain. These interactions resulted in deacetylation of histones Ac-H3 and Ac-H4 at the proximal promoter, which is important in the transcriptional repression of p21. MTT (3-(4,5-di meth yl thi azol-2-yl)-2,5-diphenyltetrazolium bromide) assays and fluorescent-activated cell sorter analysis revealed that ZBTB5 stimulated both cell proliferation and cell cycle progression, significantly increasing the number of cells in S-phase. Overall, our data suggest that ZBTB5 is a potent transcription repressor of cell cycle arrest gene p21 and a potential proto-oncogene stimulating cell proliferation
Files in This Item:
T200901294.pdf Download
DOI
10.1074/jbc.M109.025817
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Yun, Chae Ok(윤채옥)
Jeon, Bu Nam(전부남)
Choi, Won Il(최원일)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103885
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