Transcription of the PSMD4 gene is upregulated in hypoxia in prostate cancer cells

Abstract

ThePSMD4(Proteosome 26S non-ATPase subunit 4) gene islocated human chromosome 1. This gene encodes three proteins,namely S5A, antisecretory factor (ASF) and Angiocidin. S5a isthe polyubiquitin binding subunit of the 26S proteasome. ASF isa plasma-bound protein known to inhibit cholera toxin-inducedintestinal fluid secretion in rats. Most importantly, Angiocidin isa protein over-expressed in many different solid tumors.Hypoxia is a critical stimulus in many physiological and dis-ease states like cancer. In addition, regulation studies of thePSMD4gene are rather limited. The aim of the study is to iden-tify the hypoxic regulation of thePSMD4gene. For transcrip-tional regulation of thePSMD4gene, the truncated promoterconstructs were cloned into a luciferase-based expression vector.Basal transcriptional activities of the promoter constructs weredetermined in normoxic and hypoxic conditions in PC3 (prostatecell line). We found that the 262 bp promoter construct ( 191/+65) was affected by hypoxia. Bioinformatics analysis also revealsthat the promoter of thePSMD4gene contains several putativeHREs (Hypoxia Response Element) that is a target of HIF1atranscription factor. The expression of thePSMD4gene was alsodetermined at mRNA and protein level.