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Molecular and Cellular Biochemistry

, Volume 327, Issue 1–2, pp 53–63 | Cite as

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

  • Masayoshi Yamaguchi
Article

Abstract

RGPR-p117 was originally discovered as a novel protein that binds to a nuclear factor I (NFI) consensus motif TTGGC(N)6CC, 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.

Keywords

RGPR-p117 Regucalcin Transcription factor Nuclear localization Apoptosis 

Notes

Acknowledgments

The author was supported in part by a Grant-in-Aid for Scientific Research (C) No. 08672522, No. 10672048, and No. 17590063 from the Ministry of Education, Science, Sports, and Culture, Japan.

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© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Division of Endocrinology and Metabolism and Lipids, Department of MedicineEmory University School of MedicineAtlantaUSA

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