Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step in hepatic gluconeogenesis. Glucagon (via the second messenger cAMP) and glucocorticoids stimulate the transcription of the PEPCK gene, whereas insulin and phorbol esters inhibit, in a dominant fashion, these effects. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, prevents the stimulation of glycogen synthesis, glucose transport, mitogen-activated protein kinase, and p70/p85 ribosomal S6 protein kinase by insulin. We now show that wortmannin can also block the inhibition of glucocorticoid- and cAMP-stimulated PEPCK gene expression by insulin. PEPCK-chloramphenicol acetyltransferase fusion gene experiments demonstrate that wortmannin blocks an activity that is required for insulin signaling to elements within the PEPCK promoter. Phorbol esters mimic the action of insulin on the regulation of PEPCK gene expression, but wortmannin does not block the effect of these agents. Thus, phosphatidylinositol 3-kinase is required for the regulation of PEPCK gene expression by insulin, but not by phorbol esters. The immunosuppressant rapamycin, a potent inhibitor of insulin or phorbol ester stimulation of p70/p85 ribosomal S6 protein kinase, has no significant effect on the regulation of PEPCK gene expression by insulin or phorbol esters. Thus, p70/p85 ribosomal S6 protein kinase does not have a role in signaling to the PEPCK promoter by insulin or phorbol esters.
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PMID:Phosphatidylinositol 3-kinase, but not p70/p85 ribosomal S6 protein kinase, is required for the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin. Dissociation of signaling pathways for insulin and phorbol ester regulation of PEPCK gene expression. 779 43

We have identified and analyzed a 27-nucleotide sequence (U5 repressive element, designated as U5RE) at the U5 region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) which is required for HTLV-I basal transcriptional repression. The basal promoter strength of constructs that contained deletions in the U5 region of the LTR was analyzed by chloramphenicol acetyltransferase (CAT) assays following transfection of HeLa cells or Jurkat T-cells in the presence or absence of viral transactivator tax protein. We consistently observed a 2- to 5-fold increase in basal promoter activity when sequences between +277 to +306 were deleted. In vivo competition experiments suggested that the U5 DNA fragment from +269 to +295 contains a functional repressive element (U5RE). Using gel mobility shift assays, we have purified a highly enriched fraction that could specifically bind U5RE. This DNA affinity column fraction contained three major detectable proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining: 110-, 80- and 70-kDa proteins. The 110-kDa protein appeared to be a novel DNA-binding protein whose characteristics are still obscure, while the 70- and 80-kDa proteins were shown to be related to the human autoantigen Ku, the Ku (p70/p80) complex, as demonstrated by amino acid sequencing and immunological analyses. As Ku is known to be involved in transcriptional regulation, the specific interaction of Ku with U5RE raises intriguing possibilities for its function in HTLV-I basal transcriptional repression.
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PMID:Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat. 798 30

The hexokinases, by converting glucose to glucose 6-phosphate, help maintain the glucose concentration gradient that results in the movement of glucose into cells through the facilitative glucose transporters. Hexokinase II (HKII) is the major hexokinase isoform in skeletal muscle, heart, and adipose tissue. Insulin induces HKII gene transcription in L6 myotubes, and this, in turn, increases HKII mRNA and the rates of HKII protein synthesis and glucose phosphorylation in these cells. Inhibitors of distinct insulin signaling pathways were used to dissect the molecular mechanism by which HKII gene expression is induced by insulin in L6 myotubes. Treatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), or with rapamycin, an inhibitor of the pathway from the insulin receptor to p70/p85 ribosomal S6 protein kinase (p70(s6k)), prevented the induction of HKII mRNA by insulin. In contrast, treatment with PD98059, an inhibitor of mitogen-activated protein kinase activation, had no effect on insulin-induced HKII mRNA. In addition, rapamycin blocked the insulin-induced expression of an HKII promoter-chloramphenicol acetyltransferase fusion gene transiently transfected into L6 myotubes, whereas PD98059 had no such effect. These results suggest that a phosphatidylinositol 3-kinase/p70(s6k)-dependent pathway is required for regulation of HKII gene transcription by insulin and that the Ras-mitogen-activated protein kinase-dependent pathway is probably not involved.
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PMID:Analysis of the signaling pathway involved in the regulation of hexokinase II gene transcription by insulin. 866 15

Fetal brown adipocytes cultured in a serum-free medium, containing 5 mM glucose, expressed both GLUT4 and GLUT1 glucose transporters at the mRNA and protein level. Treatment with either insulin or insulin-like growth factor (IGF)-I at physiological concentrations up-regulates the expression of the GLUT4 gene, producing a time-dependent mRNA accumulation (7-fold increase at 24 h) and a 2.5-fold increase in the amount of protein in the total membrane fraction. However, insulin treatment down-regulates GLUT1 mRNA and protein expression. Moreover, either insulin or IGF-I transactivates a full-promoter GLUT4-chloramphenicol acetyltransferase gene (CAT) construct transiently transfected to the cells, without affecting GLUT1-CAT activity. In consequence, insulin treatment for 24 h increased by 3-fold the basal glucose uptake. Inhibition of phosphoinositide (PI) 3-kinase activity with chemical agents such as wortmannin or LY294002 partially blocked insulin-induced GLUT4 mRNA accumulation, insulin-induced GLUT4 protein content, GLUT4-CAT transactivation and glucose uptake. Furthermore, co-transfection of brown adipocytes with a dominant-negative form of PI 3-kinase precluded the transactivation of the GLUT4 promoter by insulin. However, inhibition of p70S6 kinase (p70(s6k)) with rapamycin or of mitogen-activated protein kinase (MAPK) with PD098059 does not preclude insulin effects on GLUT4 gene expression or glucose uptake. Our results show for the first time a positive effect of insulin on GLUT4 gene expression in fetal brown adipocytes, suggesting the existence of insulin response element(s) in its promoter. Moreover, PI 3-kinase, but not p70(s6k) or MAPK, is an essential requirement for insulin regulation of GLUT4 gene expression.
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PMID:Insulin and insulin-like growth factor I up-regulate GLUT4 gene expression in fetal brown adipocytes, in a phosphoinositide 3-kinase-dependent manner. 989 82