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Human Kruppel-related 3 (HKR3) is a novel transcription activator of alternate reading frame (ARF) gene

Authors
 Jae-Hyeon Yoon  ;  Won-Il Choi  ;  Bu-Nam Jeon  ;  Dong-In Koh  ;  Min-Kyeong Kim  ;  Myung-Hwa Kim  ;  Jungho Kim  ;  Sujin Susanne Hur  ;  Kyung-Sup Kim  ;  Man-Wook Hur 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(7) : 4018-4031, 2014 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2014
MeSH
Cell Line, Tumor ; Cell Proliferation* ; Cyclin-Dependent Kinase Inhibitor p16/biosynthesis* ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism* ; Gene Expression Regulation/physiology* ; HEK293 Cells ; Humans ; Response Elements/physiology* ; Transcription Factors/genetics ; Transcription Factors/metabolism* ; Transcription, Genetic/physiology* ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Keywords
ARF ; Cell Cycle ; Cell Proliferation ; FBI-1 ; HKR3 ; POZ ; Transcription ; p300 ; p53
Abstract
HKR3 (Human Krüppel-related 3) is a novel POK (POZ-domain Krüppel-like zinc-finger) family transcription factor. Recently, some of the POK (POZ-domain Krüppel-like zinc finger) family proteins have been shown to play roles in cell cycle arrest, apoptosis, cell proliferation, and oncogenesis. We investigated whether HKR3, an inhibitor of cell proliferation and an uncharacterized POK family protein, could regulate the cell cycle by controlling expression of genes within the p53 pathway (ARF-MDM2-TP53-p21WAF/CDKN1A). HKR3 potently activated the transcription of the tumor suppressor gene ARF by acting on the proximal promoter region (bp, −149∼+53), which contains Sp1 and FBI-1 binding elements (FREs). HKR3 interacted with the co-activator p300 to activate ARF transcription, which increased the acetylation of histones H3 and H4 within the proximal promoter. Oligonucleotide pull-down assays and ChIP assays revealed that HKR3 interferes with the binding of the proto-oncogenic transcription repressor FBI-1 to proximal FREs, thus derepressing ARF transcription.
Full Text
http://www.jbc.org/content/289/7/4018.long
DOI
10.1074/jbc.M113.526855
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99114
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