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

cAMP increases transcription of the mitochondrial (mit.) gene for 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase, which encodes an enzyme that has been proposed as a control site of ketogenesis. The incubation of Caco-2 cells with cAMP increased mit.HMG-CoA synthase mRNA levels 4-fold within 24 h. We have identified an active cAMP-response element (CRE) located 546 bp upstream of the mit. HMG-CoA synthase promoter that is necessary for the induction of expression by dibutyryl cAMP. Co-transfections of constructs, containing the CRE element of the mit.HMG-CoA synthase promoter fused to the gene for chloramphenicol acetyltransferase, with protein kinase A and a dominant-negative mutant of cAMP-response-element-binding protein (CREB) show that the response to cAMP is mediated by the transcription factor CREB. The CRE element confers responsiveness of protein kinase A to a heterologous promoter in transfection assays in Caco-2 cells. Gel-retardation assays revealed that the mit.HMG-CoA synthase CRE binds to recombinant CREB. The shifted band obtained with the putative mit. HMG-CoA synthase CRE sequence and nuclear proteins from Caco-2 cells competed with CRE sequences of other genes such as somatostatin and phosphoenolpyruvate carboxykinase. We conclude that the regulation of the expression of the gene for mit.HMG-CoA synthase in Caco-2 cells by cAMP is mediated by a CRE sequence in the promoter.
 ...
PMID:Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase promoter contains a CREB binding site that regulates cAMP action in Caco-2 cells. 1062 Apr 95

Dihydrolipoamide dehydrogenase is a common component of four multienzyme complexes which are involved in oxidation of carbohydrates, lipids and amino acids. To better understand the regulation of human DLD gene expression, we have analyzed the proximal promoter region of this gene. DNase I footprinting analysis of the promoter region (-322 to +47 bp) revealed four major protein-binding domains (termed P1-P4). Nested deletions and site-specific mutations of approximately 100 bp proximal promoter region identified two elements, TACGAC direct repeat sequence and cAMP-response element (CRE)-like site, which are localized in the P2 and P1 domains, respectively, and mediate basal transcription of the DLD gene. Electrophoretic mobility supershift assays showed that the CRE-like site is associated with CRE binding protein. Interestingly, when DLD promoter constructs (-1.8 kb to +47 bp and -78 to +47 bp) fused with the chloramphenicol acetyltransferase (CAT) reporter gene were transiently transfected into human HepG2 cells either in the presence or absence of 0.5 mM 8-Br-cAMP, the levels of CAT expression remained unaffected. In addition, endogenous DLD mRNA levels in HepG2 cells also remained unaffected by treatment with 0.5 mM 8-Br-cAMP. These results indicate that the CRE binding protein is essential for basal transcription of the human DLD promoter, but does not confer cAMP-dependent gene regulation.
 ...
PMID:Human dihydrolipoamide dehydrogenase gene transcription is mediated by cAMP-response element-like site and TACGAC direct repeat. 1146 32


<< Previous 1 2