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

Abstract

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) 6 CC 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.

Transcriptional regulation of the ER stress-inducible gene Sec16B in Neuro2a cells

“…Since the ER is an important organelle that controls the synthesis and transport of various lipids [26], it is possible that certain mutations in the Sec16B protein influence lipid homeostasis within the ER to trigger obesity. In addition, the Sec16B gene is also called a Regucalcin gene promoter region-related protein-p117 (RGPR-117) [27], and this Sec16B/RGPR-117 is reported to act as a transcription factor within the nucleus. Therefore, further functional characterization of Sec16B might help to elucidate intracellular homeostasis beyond the ER.…”

Association of Plant-Based and High-Protein Diets with a Lower Obesity Risk Defined by Fat Mass in Middle-Aged and Elderly Persons with a High Genetic Risk of Obesity

“…The third member of the best model group, SEC16B _rs509325, is a variant of the SEC16B gene, also known as RGPR -p117, a gene that encodes a protein known as regucalcin that is characterized by its leucine zipper motif. Regucalcin is known to be a transporter of proteins from the endoplasmic reticulum, but evidence to date has not demonstrated the role of the transporter in lipid metabolism [ 31 ]. Nevertheless, variants of the SEC16B gene have consistently been shown to be linked to human obesity, especially in Asian populations [ 3 , 32 ].…”

Plant-based and high protein diets are associated with a lower risk of obesity among Koreans at a high genetic risk of obesity.

“…The third member of the best model group, SEC16B_rs509325, is a variant of the SEC16B gene, also known as RGPR-p117, a gene that encodes a protein known as regucalcin that is characterized by its leucine zipper motif. Regucalcin is known to be a transporter of proteins from the endoplasmic reticulum, but evidence to date has not demonstrated the role of the transporter in lipid metabolism [27]. Nevertheless, variants of the SEC16B gene have consistently been shown to be linked to human obesity, especially in Asian populations [3,28].…”