Human Kruppel-related 3 (HKR3) is a novel transcription activator of alternate reading frame (ARF) gene.
HKR3 (Human Krueppel-related 3) is a novel POK (POZ-domain Krueppel-like zinc-finger) family transcription factor. Recently, some of the POK (POZ-domain Krueppel-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.
Mesh Terms:
Cell Line, Tumor, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p16, DNA-Binding Proteins, Gene Expression Regulation, HEK293 Cells, Humans, Response Elements, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53
Cell Line, Tumor, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p16, DNA-Binding Proteins, Gene Expression Regulation, HEK293 Cells, Humans, Response Elements, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53
J. Biol. Chem.
Date: Feb. 14, 2014
PubMed ID: 24382891
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