Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription from the ASNS (asparagine synthetase) gene is increased in response to either amino acid (amino acid response) or glucose (endoplasmic reticulum stress response) deprivation. These two independent pathways converge on the same set of genomic cis-elements within the ASNS promoter, referred to as nutrient-sensing response element-1 and -2. Chromatin immunoprecipitation analysis provides the first in vivo evidence for activating transcription factor (ATF)-3 binding to the proximal ASNS promoter containing the nutrient-sensing response element-1 sequence. Overexpression of the full-length ATF3 protein caused a concentration-dependent biphasic response in ASNS promoter-driven transcription. Both amino acid limitation and activation of the endoplasmic reticulum stress response by glucose deprivation caused an increase in ATF3 mRNA content. However, reverse transcriptase-PCR analysis revealed that the increase in the ATF3 mRNA species detected by Northern analysis actually encoded both full-length ATF3 and two predicted truncated ATF3 isoforms (ATF3deltaZip2c and ATF3deltaZip3). Based on sequence analysis, one of the predicted truncated proteins (ATF3deltaZip3) is likely incapable of binding DNA; and yet, exogenous expression of the cDNA enhanced starvation-induced or ATF4-activated ASNS transcription, possibly by sequestering corepressor proteins. Collectively, the results provide evidence for a potential role of multiple predicted ATF3 isoforms in the transcriptional regulation of the ASNS gene in response to nutrient deprivation.
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PMID:Amino acid deprivation and endoplasmic reticulum stress induce expression of multiple activating transcription factor-3 mRNA species that, when overexpressed in HepG2 cells, modulate transcription by the human asparagine synthetase promoter. 1288 27

Hypospadias is a penile developmental abnormality that may partly result from in utero exposure to estrogenic compounds. Expression of activating transcription factor 3 (ATF3) is elevated in human foreskin tissue from hypospadic patients, and in utero exposure to ethinyl estradiol (17-EE) causes ATF3 upregulation in a hypospadias mouse model. We investigated the effects of in vitro exposure to EE on ATF3 expression and promoter activity in human foreskin fibroblasts using immunocytochemistry, quantitative polymerase chain reaction (PCR), western blot, and the luciferase activity assay. Immunocytochemistry showed peak positive staining at 2 hours after 0.5 to 3 hours of EE treatment (0.1 microM). Western blot showed significantly increased ATF3 protein expression (P = 0.006) after EE exposure. ATF3 mRNA, as evaluated using reverse transcriptase PCR and TaqMan real-time PCR, also increased (P = 0.146). In addition, the luciferase activity assay showed that ATF3 promoter activity was significantly enhanced after 1 hour of EE exposure (P < 0.0001). Thus, EE upregulates ATF3 expression in fibroblasts in vitro, consistent with our previous results with human tissue and in vivo mouse models. ATF3 is involved in the TGF-beta epithelial-mesenchymal signaling pathway, and its involvement in hypospadias suggests that ATF3 plays a role in development of this anomaly as a result of exposure to estrogenic compounds. Its potential involvement in other manifestations of developmental endocrine disruption is worth investigating.
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PMID:Estradiol upregulates activating transcription factor 3, a candidate gene in the etiology of hypospadias. 1800 Nov 66