Novel protein RGPR-p117: its role as the regucalcin gene transcription factor

Abstract

RGPR-p117 was originally discovered as a novel protein that binds to a nuclear factor I (NFI) consensus motif TTGGC(N)(6)CC, which is present in the 5'-flanking region of the regucalcin gene (rgn). RGPR-p117 has been identified in human, rat, mouse, bovine, rabbit, and chicken livers. Phylogenetic analysis of six vertebrates shows that RGPR-p117 appears to form a single cluster, indicating a common evolutionary relationship of the RGPR-p117 family. The RGPR-p117 gene consists of at least 26 exons spanning approximately 4.1 kbp and is localized on human chromosome 1q25.2. RGPR-p117 mRNA is expressed in the liver, kidney, heart, spleen, and brain of rats. RGPR-p117 mRNA expression is stimulated through signaling mechanisms. Mammalian RGPR-p117 conserves a leucine zipper motif, which is present in many gene regulatory proteins. RGPR-p117 has been shown to translocate from the cytoplasm to the nucleus in NRK52E cells, a process which is mediated through protein kinase C signaling following hormonal stimulation. The phosphorylated RGPR-p117 binds to the TTGGC motif in the promoter region of the regucalcin gene and enhances regucalcin mRNA expression in the cells, indicating a role as a transcriptional factor. RGPR-p117 is also localized in the plasma membranes, nucleus, mitochondria, microsomes, and cytoplasm. Overexpression of RGPR-p117 has been found to induce a significant decrease in protein and DNA contents in cells, suggesting that RGPR-p117 may regulate the gene expression of other related proteins as well as the transcription factor. Also, overexpression of RGPR-p117 has a suppressive effect on cell death by inhibiting the gene expression of caspase-3, caspase-8, and Fas-associating death domain protein whose TTGGC motif is present in the promoter region of their genes. The novel protein RGPR-p117 has been shown to play an important role as a transcription factor.