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)

Characterization of the human insulin-like growth factor binding protein-1 (IGFBP-1) promoter was initiated to facilitate study of developmental and hormonal factors regulating IGFBP-1 production. The region immediately 5' to the IGFBP-1 mRNA capsite is typical of a eukaryotic promoter, with a TATA sequence beginning 28 base pairs (bp) and a CCAAT promoter element beginning 72 bp upstream from this capsite. A 1.3-kilobase insert containing the IGFBP-1 capsite and 1205 bp of this putative IGFBP-1 promoter region directs expression of the reporter gene chloramphenicol acetyltransferase (CAT) in an orientation-specific manner in transfected HEP G2 cells, and the capsite identified for the CAT mRNA is identical to that identified for native IGFBP-1 mRNA. These observations suggest that the 1.3-kilobase insert contains the IGFBP-1 promoter. This promoter was further characterized by deletion analysis, site-directed mutagenesis, gel mobility shift assays, and DNaseI protection assays. These studies identify the CCAAT box region as the major cis element involved in basal IGFBP-1 promoter activity in HEP G2 cells, demonstrate that increased basal promoter activity is associated with the binding of at least one HEP G2 nuclear factor to the CCAAT box region, and indicate that the DNA binding factor(s) responsible for increased basal promoter activity is related to liver factor B1. These observations suggest that liver B1 is the major trans-acting factor stimulating basal IGFBP-1 promoter activity in HEP G2 cells.
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PMID:The promoter of the human gene for insulin-like growth factor binding protein-1. Basal promoter activity in HEP G2 cells depends upon liver factor B1. 170 Nov 75

Insulin rapidly lowers serum insulin-like growth factor-binding protein-1 (IGFBP-1) levels in vivo. In studies reported here, HEP G2 cells were used as a model system to investigate how insulin achieves this effect. When HEP G2 cells were incubated with 100 nM insulin for 6, 14, or 24 h, IGFBP-1 protein levels in conditioned medium fell to approximately 50% of control values. This apparently was due to a fall in the rate of IGFBP-1 protein synthesis, since HEP G2 cells incorporated 46% less [35S]methionine into IGFBP-1 during a 4-h incubation with 100 nM insulin. IGFBP-1 mRNA levels were similarly affected by 100 nM insulin, falling to 45% of control values after 2 h, and to 9% of control values after 4 h of incubation with this hormone. The fall in IGFBP-1 mRNA level is consistent with data from nuclear transcription assays. HEP G2 nuclei isolated from cells that were incubated with 100 nM insulin for 2 h synthesized only approximately 1/3 the number of IGFBP-1 transcripts as did control nuclei. Further evidence that insulin decreases IGFBP-1 gene transcription comes from transient transfections using chimeric IGFBP-1 promoter-chloramphenicol acetyltransferase reporter gene constructs. IGFBP-1 promoter activity fell to approximately 50% of control values when HEP G2 cells transfected with a construct containing the first 1205 base pairs of the IGFBP-1 promoter were incubated with 100 nM insulin for 6, 14, or 24 h. Insulin lowered both IGFBP-1 protein levels and promoter activity in a dose-dependent manner. A half-maximal effect was found at approximately 1 nM insulin and a maximal effect was found at approximately 10 nM insulin in each instance. Transfections with constructs containing smaller IGFBP-1 promoter fragments showed that the region spanning from 103 to 529 base pairs 5' to the IGFBP-1 mRNA cap site was necessary to demonstrate the inhibitory effect of insulin. These studies indicate that insulin lowers IGFBP-1 protein levels, at least in part, by rapidly decreasing the rate of IGFBP-1 gene transcription, and suggest that this insulin-mediated fall in transcription is conferred through a specific region of the IGFBP-1 promoter.
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PMID:Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1. 171 56

Insulin-like growth factor binding protein-1 (IGFBP-1) is expressed primarily in the liver, kidney, and uterus. Basal IGFBP-1 promoter activity in human HEP G2 hepatoma cells is dependent upon a proximal promoter element that binds hepatic nuclear factor 1 (HNF1), a protein that is likely to be an important factor regulating the expression of many genes in liver and kidney. To test whether HNF1 activates IGFBP-1 transcription, HEP G2 cells and HeLa cells were cotransfected transiently with HNF1 expression vectors and with IGFBP-1 promoter/chloramphenicol acetyltransferase reporter gene constructs. HNF1 increased IGFBP-1 promoter activity in both HEP G2 and HeLa cells. Gel mobility-shift assays and additional transfections in HeLa cells showed that expressed full-length and carboxy-terminal truncated forms of HNF1 could each bind the HNF1 cis element of the IGFBP-1 promoter; however, significant trans-activation only occurred in the presence of the full-length HNF1 protein, similar to past experience with these two HNF1 forms and the albumin promoter. Further studies showed that IGFBP-1 promoter constructs containing mutations with high or low affinity for HNF1 responded to HNF1 expression with increased or decreased activity, respectively, relative to the native promoter. These studies suggest that HNF1 and/or related proteins play a role in hepatic, and perhaps also renal, expression of IGFBP-1.
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PMID:HNF1 activates transcription of the human gene for insulin-like growth factor binding protein-1. 768 29