title: Human Kruppel-related 3 (HKR3) is a novel transcription activator of alternate reading frame (ARF) gene.
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.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Korea.
authors.forename: Jae-Hyeon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Choi
authors.forename: Bu-Nam
authors.initials: BN
authors.lastname: Jeon
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Koh
authors.forename: Min-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Myung-Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Jungho
authors.initials: J
authors.lastname: Kim
authors.forename: Sujin Susanne
authors.initials: SS
authors.lastname: Hur
authors.forename: Kyung-Sup
authors.initials: KS
authors.lastname: Kim
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D020218:Response Elements / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C100846:ZBTB48 protein, human
keywords: ARF; Cell Cycle; Cell Proliferation; FBI-1; HKR3; POZ; Transcription; p300; p53