Glucose-Regulated Protein (GRP94 and GRP78) Genes Share Common Regulatory Domains and Are Coordinately Regulated by Common trans-Acting Factors

Abstract

We isolated the promoter of the human gene encoding the 94,000-dalton glucose-regulated protein (GRP94). The 5′-flanking region Important for its expression was identified by deletion analysis. Comparison of the promoters of the genes for GRP78 and GRP94 derived from human, rat, and chicken cells revealed a common domain of 28 base pairs within the putative regulatory regions of both genes. This domain has been shown to interact with protein factors in the promoter of the gene for GRP78. Since the genes for GRP94 and GRP78 are transcriptionally regulated with similar kinetics under a variety of stress conditions, we are interested in examining the possible mechanisms for their coordinated expression. Through in vitro and in vivo competition assays, we found that the protein factors which interact with the promoter of the gene for GRP94 also have affinity for the conserved domain of the promoter of the gene for GRP78. These findings suggest that the genes for GRP94 and GRP78 are coordinately regulated through common trans-acting factors which recognize a common regulatory domain of glucose-regulated protein gene promoters.