Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sequence 5'-GTGGGTGTGGC (G3T) is important for the efficient initiation of transcription from the human ADH2 promoter. We show here that the purified transcription factor Sp1 binds with high affinity to the G3T site of ADH2 (encoding beta beta-alcohol dehydrogenase), even though the G3T sequence does not contain the canonical Sp1-binding site, GGGCGG. Proteins from mouse liver nuclei and purified Sp1 both footprint the same sequence of the ADH2 promoter with similar patterns. UV crosslinking demonstrates that the major G3T-binding protein in the liver extract is similar in size to Sp1. Mouse liver nuclear extract resembles purified Sp1 in its relative binding affinity to a series of oligodeoxyribonucleotides containing either the Sp1-binding site or variants of the G3T sequence. These data indicate that the G3T sequence can interact with Sp1 and that Sp1 may be important in the expression of ADH2. The G3T sequence from the closely related ADH3 gene (encoding gamma gamma-alcohol dehydrogenase) differs from that of ADH2 in the first two nucleotides; it binds both the liver protein and purified Sp1 with lower affinity. This might explain why ADH3 is expressed at lower levels than ADH2 in the liver.
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PMID:Expression of the human ADH2 gene: an unusual Sp1-binding site in the promoter of a gene expressed at high levels in liver. 144 29

The insulin-like growth factor I receptor (IGF-I-R) gene is expressed in most body tissues. The levels of IGF-I-R mRNA, however, are regulated by a number of physiological conditions (development, differentiation, and hormonal milieu) as well as in certain pathological states (diabetes and tumors). To understand the molecular mechanisms which control the transcription of the IGF-I-R gene, we have cloned the promoter of the rat receptor gene and have characterized its activity by transient expression assays. Different fragments of the 5'-flanking region (subcloned upstream of a luciferase reporter gene) were transfected into buffalo rat liver 3A cells (a cell line with a low number of IGF-I binding sites) and Chinese hamster ovary cells (a cell line with a higher number of cell-surface receptors). In both cell lines, most of the promoter activity was located in the proximal 416 base pairs of 5'-flanking region. However, further dissection of this proximal fragment revealed a cell type-specific pattern of promoter activity. Thus, in buffalo rat liver 3A cells, subfragments of this region each contributed to total activity, suggesting that contiguous cis-elements can act together to activate transcription. In Chinese hamster ovary cells, on the other hand, subfragments of the proximal promoter region partially substituted for the proximal 416 base pairs of 5'-flanking region. Coexpression studies using an IGF-I-R promoter reporter construct together with an Sp1 expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Sp1. The results obtained showed that Sp1 can trans-activate the IGF-I-R promoter in vivo. Transient transfection assays were complemented with gel-retardation assays and DNase I footprinting experiments, which showed that transcription factor Sp1 is potentially an important regulator of IGF-I-R gene expression.
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PMID:Structural and functional analysis of the insulin-like growth factor I receptor gene promoter. 144 10