Pulmonary Arterial Hypertension KnowledgeBase (bioinfom_tsdb)
bioinfom_tsdb
Pulmonary Arterial Hypertension KnowledgeBase
General information | Literature | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID

3104

Name

ZBTB48

Synonymous

HKR3|ZNF855|pp9964;zinc finger and BTB domain containing 48;ZBTB48;zinc finger and BTB domain containing 48

Definition

GLI-Kruppel family member HKR3|krueppel-related zinc finger protein 3|zinc finger and BTB domain-containing protein 48|zinc finger protein 855

Position

1p36.3

Gene type

protein-coding

Title

Abstract

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

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 tumor suppressor gene ARF by acting on the proximal promoter region (bp, -149 approximately +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.

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