Human Kruppel-related 3 (HKR3) is a novel transcription activator of alternate open reading frame (ARF) gene [Cell Biology]

January 1st, 2014 by Yoon, J.-H., Choi, W.-I., Jeon, B.-N., Koh, D.-I., Kim, M.-K., Kim, M.-H., Kim, J., Hur, S. S., Kim, K.-S., Hur, M.-W.

HKR3 (Human Kruppel-Related 3) is a novel POK (POZ-domain Kruppel-like zinc finger) family transcription factor. Recently, some of the POK (POZ-domain Kruppel-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 tumour 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 coactivator 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.