Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progesterone receptor (PR) functions as a transcription factor that modulates the transcription of target genes in response to progesterone and other signals. The transcriptional activity of PR requires the involvement of coactivators such as steroid receptor coactivator-1 (SRC-1). To dissect the role of SRC-1 in PR transactivation, we established an in vitro transcription system with chromatin templates, in which PR induced transcription in a ligand-dependent and PRE-dependent manner. In the presence of ligand, purified PR bound to chromatin templates, resulting in chromatin remodeling. With this system, the ability of purified SRC-1 to act as a coactivator of PR was examined. SRC-1 potentiated transcription by ligand-activated PR, whereas it had no effect on transcription in the absence of ligands. As SRC-1 possesses intrinsic histone acetyltransferase activity, we tested the role of acetylation in PR-mediated transcription by using a histone deacetylase inhibitor, trichostatin A (TSA). We found that addition of TSA strongly enhanced PR-dependent transcription on chromatin but not on naked DNA template, and the effects of SRC-1 and TSA on PR transactivation were partially redundant. In addition, SRC-1 was able to potentiate PR transactivation with nonchromatin templates. Thus, our results substantiate a two-step mechanism whereby recruitment of coactivator SRC-1 by the ligand-activated PR in vivo leads to (i) chromatin remodeling through histone acetylation and (ii) recruitment/stabilization of the preinitiation complex.
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PMID:Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin. 1044 19

To better understand the structure and the function of ovine glucose 6-phosphate dehydrogenase (G6PD) promoter region, a genome-walking procedure was followed to isolate and sequence a 1628 bp fragment, containing the 5' regulatory region of the G6PD gene. In silico analysis of the sequence showed many conserved blocks and features with other known mammalian G6PD promoter regions. The analysis also revealed the presence of one TATA box, three GC boxes, two E-boxes and several binding sites for Stimulating Protein 1 (Sp1) and Activator Protein 2 (AP2). Moreover, elements involved in the regulation of lipogenesis like USF (Upstream stimulating factor), HSF (Heat Shock Factor), F2F (Prolactin receptor), RAR (Retinoid Acid Receptor), STRE (STress Response Element), RORa (Retinoid related Orphan Receptor alpha), GATA (GATA binding factor), RFX (Regulatory Factor X), SREBP (Sterol Regulatory Element Binding Protein), MEP (Metal Element Protein), CREB (insulin receptor), PRE (Progesterone receptor), and HNF4 (Hepatic Nuclear Factor 4) were detected. The most important regulatory motifs were found to be conserved as compared to those in human and mouse counterparts. However, some differences were noted, likely indicating differences in the transcription regulation of G6PD gene between ruminant and non-ruminant species.
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PMID:Cloning, characterization and computational analysis of the 5' regulatory region of ovine glucose 6-phosphate dehydrogenase gene. 1749 56

Progesterone receptor (PR) and its specific ligand play a key role in development and physiology of mammary gland. The role of PR in initiation and progression of breast carcinoma (BCa) is unquestionable, although molecular mechanism of PR action is complex and not fully understood. It is known that increased risk of breast cancer is associated with progestin-based (synthetic ligands of progesterone) hormonal contraception or hormone replacement therapies. It is estimated that ER/PR-positive tumours represent approximately 50-70% of all BCa cases, and the loss of PR is associated with resistance to hormonal therapy and increased tumour invasiveness. In classical, genomic signalling pathway cytoplasmic PR, following ligand binding, translocates to the nucleus and regulates expression of genes with the PRE sequence. PR is also involved in a large number of alternative, non-genomic signalling cascades, e.g. PR is able to activate MAPK and PI3K/AKT pathways, which leads to regulation of gene expression. The cross-talk between PR and Growth Factors Receptors (GFR) results in progesterone-independent activation of PR as well as PR-regulated GFR expression and activation. Growth factors signalling promotes formation of a pool of hypersensitive PR responsive to even very low ligand concentration. Transcriptional activity of PR as well as its dynamic impact on processes such as cell migration and adhesion are crucial for BCa progression. Further studies of multifaceted mechanisms of PR action may contribute to new PR-targeting therapeutic strategies for breast cancer patients.
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PMID:[Aspects of progesterone receptor (PR) activity regulation - impact on breast cancer progression]. 2668 13