Involvement of regucalcin gene promoter region-related protein-p117, a transcription factor, in human obesity.

Abstract

Regucalcin gene promoter region-related protein-p117 (RGPR-p117; gene symbol, rgpr-117) was identified in 2001 as a novel transcription factor that specifically binds to a nuclear factor I consensus motif, TTGGC(N)6CC in the promoter region of the regucalcin (rgn) gene. The human RGPR-p117 gene consists of 26 exons spanning ~4.1 kbp and is localized on chromosome 1q25.2. The nuclear translocation of cytoplasm RGPR-p117 is mediated via the protein kinase C-dependent signaling pathway. Overexpression of RGPR-p117 enhances the transcription activity of rgn, and a protective effect on cell death by inhibition of gene expression levels of caspase-3, caspase-8 and FADD proteins that possess the TTGGC motif in the promoter region of those genes was revealed. RGPR-p117 has a crucial role as a transcription factor. Notably, RGPR-p117 was shown to localize in the plasma membranes, mitochondria and microsomes (endoplasmic reticulum; ER). RGPR-p117, which is located in the ER, was also shown to have a role as an ER export factor implicated in the transports of proteins and lipids. As a result of this finding, it was proposed in 2007 that RGPR-p117 is renamed SEC 16 homolog B, endoplasmic reticulum export factor (SEC16B). Recently, there is increasing evidence that RGPR-p117/SEC16B may be involved in human obesity. Thus, the current review presents data regarding the involvement of RGPR-p117 in human obesity.