Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 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. The role of RGPR-p117 in cell function has not been fully clarified. This study was undertaken to determine whether overexpression of RGPR-p117 regulates various types of signaling factor-induced apoptotic cell death in the cloned normal rat kidney proximal tubular epithelial NRK52E cells. NRK52E cells (wild-type) or stable RGPR-p117/phCMV2-transfected cells (transfectant) were cultured in Dulbecco's modified Eagle's medium containing 5% bovine serum (BS). NRK52E cells with subconfluent monolayers were cultured for 24-72 h in a medium without BS. The presence of tumor necrosis factor-alpha (TNF-alpha; 1.0 or 10 ng/ml of medium), lipopolysaccharide (LPS; 0.1 or 1.0 microg/ml), Bay K 8644 (10(-6) or 10(-5) M), or thapsigargin (10(-8) or 10(-7) M) caused a significant decrease in the number of NRK52E wild-type cells or phCMV2-transfected (mock-type) cells. The effect of TNF-alpha, LPS, Bay K 8644, or thapsigargin in decreasing cell number was significantly suppressed in the presence of the caspase-3 inhibitor (10(-8) M) in wild-type cells cultured for 48 h. The effect of TNF-alpha, LPS, or Bay K 8644 in decreasing cell number was significantly inhibited in the transfectants, while the effect of thapsigargin on cell death was not inhibited in the transfectants. Culture with TNF-alpha or LPS caused DNA fragmentation in wild-type cells. These effects were significantly suppressed in the transfectants. The result of reverse transcription-polymerase chain reaction analysis using specific primers for the genes of apoptotic cell death-related proteins showed that IAP-1, FADD, caspase-8, caspase-9, and caspase-3 mRNA levels were significantly decreased in the transfectants, while Akt-1, Bid, Apaf-1, and glyceroaldehyde-3-phosphate dehydrogenase mRNA levels were not significantly altered in the transfectants. Culture with TNF-alpha, LPS, Bay K 8644, or thapsigargin caused a significant increase in Apaf-1 or caspase-3 mRNA levels. Such an effect was not seen in the transfectants. This study demonstrates that overexpression of RGPR-p117 has a suppressive effect on cell death and apoptosis induced by TNF-alpha, LPS, or Bay K 8644 whose actions are mediated through intracellular signaling pathways. This study also demonstrates that RGPR-p117 regulates the gene expression of apoptosis-related proteins.
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PMID:Overexpression of RGPR-p117 suppresses apoptotic cell death and its related gene expression in cloned normal rat kidney proximal tubular epithelial NRK52E cells. 1778 89

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