Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel protein RGPR-p117 was discovered as a regucalcin gene promoter region-related protein that binds to the TTGGC motif using a yeast one-hybrid system. Whether overexpression of RGPR-p117 can modulate gene expression in the cloned normal rat kidney proximal tubular epithelial NRK52E cells was investigated. NRK52E cells (wild-type) or HA-RGPR-p117/phCMV2-transfected NRK52E cells were cultured in Dulbecco's minimum essential medium (DMEM) containing 5% bovine serum (BS). Proliferation of NRK52E cells (wild-type) was not significantly altered by overexpression of HA-RGPR-p117. The expression of rat regucalcin, alpha-fetoprotein, albumin, glucokinase, 11beta-hydroxy-steroid dehydrogenase, phosphoenolpyruvate carboxykinase, which contains TTGGC motif in the promoter region of their genes, was seen in NRK52E cells (wild-type) by using reverse transcription-polymerase chain reaction (RT-PCR). Of these genes, regucalcin mRNA levels were significantly enhanced in transfectants. The expression of p21 or glycero-aldehyde-3-phosphate dehydrogenase mRNA was not significantly changed in transfectants. The results of Western blot analysis showed that regucalcin protein was significantly increased in transfectants. The enhancement of regucalcin mRNA expression in transfectants was significantly suppressed in the presence of staurosporine (10(-10) M), an inhibitor of protein kinase C. This enhancement was not significantly changed in the presence of dibucaine (10(-8) M), PD98059 (10(-8) M) or vanadate (10(-6) M). This study demonstrates that overexpression of RGPR-p117 enhances the expression of regucalcin mRNA and its protein level in NRK52E cells. RGPR-p117 may play a role as a transcriptional factor.
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PMID:Overexpression of RGPR-p117 enhances regucalcin gene expression in cloned normal rat kidney proximal tubular epithelial cells. 1627 85

In this study we investigated whether the nuclear localization of regucalcin in cloned normal rat kidney tubular epithelial NRK52E cells is regulated after culture with hormonal signaling factors. Stable regucalcin/pCXN2 transfectants with subconfluent monolayers were further cultured for 24 or 48 h in a serum-free medium containing either vehicle, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), parathyroid hormone (PTH), phorbol 12-myristate 13-acetate (PMA), or other factors. Culture with TNF-alpha (1.0 ng/ml of medium) or TGF-beta1 (5.0 ng/ml) for 48 h caused a significant decrease in regucalcin mRNA levels in NRK52E cells (wild-type), while regucalcin mRNA levels were markedly increased in the presence of PMA (10(-6) M), an activator of protein kinase C, in wild-type cells. Immunocytochemical observation showed that HA-regucalcin was markedly localized in the nucleus of HA-regucalcin/ phCMV2-transfected cells. The nuclear localization was enhanced in culture with BS (5%), PTH (10(-7) M), Bay K 8644 (2.5x10(-6) M), or PMA (10(-6) M) for 24 or 48 h. Culture with staurosporine, an inhibitor of protein kinase C, caused a remarkable decrease in the localization of HA-regucalcin in the nucleus of HA-RGPR-p117/phCMV2-transfected cells with PMA. Culture with PMA (10(-6) M) for 24 or 48 h caused a remarkable increase in nuclear regucalcin protein levels. The effect of PMA in increasing nuclear regucalcin levels was completely absent in culture with staurosporine (10(-8) M). The nuclear localization of regucalcin in the stable regucalcin/pCXN2-transfected cells (transfectant) increased markedly as compared with that of wild-type cells, whereas the increase was less evident in the transfectants cultured with staurosporine. This study demonstrated that regucalcin localizes in the nucleus of cloned normal rat kidney proximal tubular epithelial NRK52E cells, and that its nuclear localization is enhanced through an intracellular signaling process which involves protein kinase C.
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PMID:Nuclear localization of regucalcin is enhanced in culture with protein kinase C activation in cloned normal rat kidney proximal tubular epithelial NRK52E cells. 1842 53

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.
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PMID:Novel protein RGPR-p117: its role as the regucalcin gene transcription factor. 1921 10

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.
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PMID:Involvement of regucalcin gene promoter region-related protein-p117, a transcription factor, in human obesity. 2841 34