Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously identified a silencer region in the glutathione transferase P (GST-P) gene, of which the expression is completely repressed in liver of the rat. At least three trans-acting factors bind to multiple cis-elements in this region. Since GST-P silencer 4 (GSP4) is a dominant element in this silencer, we purified the GSP4 binding protein, called Silencer Factor A (SF-A). Purified SF-A was separated into several proteins on an SDS-polyacrylamide gel, and the amino acid sequences of four major components of SF-A were determined. The amino acid sequences of three fragments were identical to those of rat NF1-L, and that of the other fragment was the same as that of hamster NF1/Red1. It is known that nuclear factor 1 (NF1) family proteins are encoded by at least four independent genes in vertebrates, and NF1-L and NF1/Red1 are derived from different genes, NFI-A and NFI-B, respectively. The microsequencing of SF-A revealed that at least two types of NF1 existed in rat liver. Functional analysis by using GAL4-fusion protein in HepG2 cells revealed that NFI-A represented the transcription activity from human metallothionein IIA promoter. Our findings indicate that multiple forms of the NF1 family bind to the silencer region and contribute to the negative regulation of the GST-P gene expression.
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PMID:Nuclear factor 1 family proteins bind to the silencer element in the rat glutathione transferase P gene. 908 12

The forkhead thyroid-specific transcription factor TTF-2 is the main mediator of thyrotropin and insulin regulation of thyroperoxidase (TPO) gene expression. This function depends on multimerization and specific orientation of its DNA-binding site, suggesting that TTF-2 is part of a complex interaction network within the TPO promoter. This was confirmed by transfection experiments and by protein-DNA interaction studies, which demonstrated that CTF/NF1 proteins bind 10 base pairs upstream of the TTF-2-binding site to enhance its action in hormone-induced expression of the TPO gene. GST pull-down assays showed that TTF-2 physically interacts with CTF/NF1 proteins. In addition, we demonstrate that increasing the distance between both transcription factors binding sites by base pair insertion results in loss of promoter activity and in a drastic decrease on the ability of the promoter to respond to the hormones. CTF/NF1 is a family of transcription factors that contributes to constitutive and cell-type specific gene expression. Originally identified as factors implicated in the replication of adenovirus, this group of proteins (CTF/NF1-A, -B, -C, and -X) is now known to be involved in the regulation of several genes. In contrast to other reports regarding the involvement of these proteins in inducible gene expression, we show here that members of this family of transcription factors are regulated by hormones. With the use of specific CTF/NF1 DNA probes and antibodies we demonstrate that CTF/NF1-C is a thyrotropin-, cAMP-, and insulin-inducible protein. Thus CTF/NF1 proteins do not only mediate hormone-induced gene expression cooperating with TTF-2, but are themselves hormonally regulated. All these findings are clearly of important value in understanding the mechanisms governing the transcription regulation of RNA polymerase II promoters, which often contain binding sites for multiple transcription factors.
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PMID:The interaction between the forkhead thyroid transcription factor TTF-2 and the constitutive factor CTF/NF-1 is required for efficient hormonal regulation of the thyroperoxidase gene transcription. 1032 30

Nuclear factor 1 (NF1) family proteins, which are encoded by four different genes (NF1-A, NF1-B, NF1-C and NF1-X), bind to the palindromic sequence and regulate the expression of many viral and cellular genes. We have previously purified NF1-A and NF1-B from rat liver as factors that bind to the silencer in the glutathione transferase P gene, and have also reported the repression domain of NF1-A. In the present study we cloned five cDNA species (NF1-B1, NF1-B2, NF1-B3, NF1-C2 and NF1-X1) and compared their expression profiles and the affinity and specificity of the DNA binding of these NF1 family members. By Northern blot analysis, we found that the expression profiles of the NF1s are indistinguishable in the various tissues of the rat. The DNA-binding affinities of NF1-A and NF1-X are higher than those of NF1-B and NF1-C, whereas all four NF1 proteins showed the same DNA-binding specificity. Transfection analyses revealed that the function of NF1-B on the transcriptional regulation differed between NF1-B isoforms and was affected by the factor(s) that bind to the promoter regions. In addition, we identified the transcriptional regulatory domain of NF1-B, which is enriched with proline and serine residues.
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PMID:Expression, DNA-binding specificity and transcriptional regulation of nuclear factor 1 family proteins from rat. 1043 16