Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously hypothesized that a mode of action of the anti-rheumatic gold salt, aurothiomalate (AuTM), is the inhibition of DNA binding by transcription factors. Studies of the progesterone receptor (PR), which has a zinc finger structure in the DNA binding domain, were consistent with this hypothesis (1). Here we show that AuTM also markedly inhibits DNA binding by the transcription factor AP-1 and has less potent effects for AP-2, NF-1 and TFIID.
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PMID:Comparative effects of gold on the interactions of transcription factors with DNA. 837 30

We have characterized the 5'-flanking region of the alpha-subunit gene of the human pyruvate dehydrogenase (E1). DNase I footprinting with rat liver nuclear extracts identified 7 major protein-binding domains termed P1 through P7 in a 796 base pair DNA fragment (base pairs -763 to +33). P1 through P4 are clustered in the -221/+33 region. These protein-binding domains contain several known consensus sequences such as a TATA box, CAAT box, Sp1, and CRE, which all have previously been implicated in the constitutive transcription of several genes. Oligonucleotide competition studies indicate that oligonucleotides specific for CTF/NF-1 and Sp1 displaced the nuclear proteins bound to the CAAT box (within P3) and an Sp1 site (within P4), respectively. Several other well-characterized and purified transactivators (c-Fos, c-Jun, C/EBP, AP-2, and Sp1) have been shown to bind to the -221/+33 region. Other elements located upstream of the -221/+33 region, which includes nuclease protection domains P5-P7, are required for enhanced promoter activity of the 796 bp sequence. Promoter activity was measured by transient expression of a chloramphenicol acetyltransferase gene ligated to deletion fragments of the 5'-flanking region. Crucial element(s) for promoter activity and complex DNA-nuclear protein interactions were confined within a region spanning -221/+33. This region also retained more than 75% of the promoter activity of the 796 bp sequence. Additionally, this promoter region shows characteristics of both facultative and housekeeping gene promoters, suggesting complex transcriptional regulation.
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PMID:Multiple protein-binding domains and functional cis-elements in the 5'-flanking region of the human pyruvate dehydrogenase alpha-subunit gene. 847 54

Tissue-type plasminogen activator (t-PA) gene expression in human endothelial cells and HeLa cells is stimulated by the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) at the level of transcription. To study the mechanism of transcriptional regulation, we have characterized a segment of the t-PA gene extending from -135 to +100 by in vivo footprinting analysis [dimethyl sulphate (DMS) method] and gel mobility shift assay. In vivo footprinting analysis revealed changes in cleavage pattern in five distinct promoter elements in both endothelial cells and HeLa cells, including a PMA-responsive element (TRE), a CTF/NF-1 binding site and three GC-boxes, and an altered cleavage pattern of the TRE and CTF/NF-1 element after PMA treatment of HeLa cells. Although endothelial cells and HeLa cells differed in the exact G residues protected by nuclear proteins,in vitro bandshift analysis showed that nuclear protein binding to the t-PA promoter was qualitatively and quantitatively very similar in both cell types, except for the TRE. Protein binding to the TRE under non- stimulated conditions was much higher in human endothelial cells than in HeLa cells, and this TRE-bound protein showed a lower dissociation rate in the endothelial cells than in HeLa cells. In endothelial cells, the proteins bound to the TRE consisted mainly of the AP-1 family members JunD and Fra-2, while in HeLa cells predominantly JunD, FosB and Fra-2 were bound. The proteins bound to the other protected promoter elements were identified as SP-1 (GC-box II and III) and CTF/NF-1 (CTF/NF-1 binding site). After PMA treatment of the cells, AP-1 and SP-1 binding was increased two-fold in endothelial cell nuclear extracts and >20-fold in HeLa nuclear extracts. In the endothelial cells, all Jun and Fos forms (c-Jun, JunB, JunD, c-Fos, FosB, Fra-1 and Fra-2) were part of the AP-1 complex after PMA induction. In HeLa cells, the complex consisted predominantly of c-Jun and the Fos family members FosB and Fra-2. In the light of previous studies involving mutational analysis of the human and murine t-PA promoter our results underline an important role of the five identified promoter regions in basal and PMA-stimulated t-PA gene expression in intact human endothelial cells and HeLa cells. The small differences in DMS protection pattern and differences in the individual AP-1 components bound in endothelial cells and HeLa cells point to subtle cell-type specific differences in t-PA gene regulation.
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PMID:Cell-type specific DNA-protein interactions at the tissue-type plasminogen activator promoter in human endothelial and HeLa cells in vivo and in vitro. 901 59

The infectious cycle of the human polyomavirus JC (JCV) is ultimately regulated in cellular nuclei at the level of viral protein expression and genomic replication. Such activity is prompted by interactions between variant nucleotide sequences within the JCV regulatory region (promoter) and cellular transcription factors that bind specific DNA consensus sites. In previous work we identified an NF-1 class member, NF-1X, as a critical transcription factor affecting the JCV cellular host range. Within variant JCV promoters, as well as other viral and cellular promoters, adjacently located NF-1 and AP-1 consensus sites are often found. The close proximity of these two binding sites suggests the opportunity for interaction between NF-1 and AP-1 proteins. Here, by electrophoretic mobility shift assays, we show temporal and dose-dependent interference by an AP-1 family member, c-Jun, upon NF-1 proteins binding an NF-1 consensus site derived from JCV promoter sequence. Moreover, as demonstrated by protein-protein interaction assays, we identify specific binding affinity independent of DNA binding between NF-1X and c-Jun. Finally, to compare the binding profiles of NF-1X and c-Jun on JCV promoter sequence in parallel with in vivo detection of viral activity levels, we developed an anchored transcriptional promoter (ATP) assay. With use of extracts from JCV-infected cells transfected to overexpress either NF-1X or c-Jun, ATP assays showed concurrent increases in NF-1X binding and viral protein expression. Conversely, increased c-Jun binding accompanied decreases in both NF-1X binding and viral protein expression. Therefore, inhibition of NF-1X binding by c-Jun appears to play a role in regulating levels of JCV activity.
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PMID:Interactions between c-Jun, nuclear factor 1, and JC virus promoter sequences: implications for viral tropism. 1692 56

The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme, also termed cytochrome P450scc, which catalyzes the conversion of cholesterol to pregnenolone in the first step of steroid biosynthesis in mitochondria. The adrenal- and gonad-selective, hormonally and developmentally regulated expression of CYP11A1 is principally driven by its 2.3 kb promoter. Multiple trans-acting factors like SF-1, Sp1, AP-2, TReP-132, LBP-1b, LBP-9, AP-1, NF-1, and Ets control CYP11A1 transcription either through DNA-protein interaction with their specific cis-acting elements or through protein-protein interaction between each other, wherein SF-1 plays a central role in adrenals and testes. In addition to binding with its proximal and upstream motifs, SF-1 also physically interacts with TFIIB, CBP/p300, TReP-132, and c-Jun/AP-1 to specifically transmit the regulatory signals of cAMP. Other factors like Sp1 family members, AP-2, and LBP-1b/LBP-9 may be other factors that play a role in CYP11A1 transcription, particularly in placental cells. The TATA sequence could also contribute to tissue-specificity and hormonal regulation of CYP11A1 transcription. This article reviews recent studies focusing on adrenals and gonads.
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PMID:Transcriptional regulation of human CYP11A1 in gonads and adrenals. 1759 37

We analyzed in detail the proximal promoter of transcription factor Sp3, which expands 281 bp from the translational start. This sequence contains putative binding sites for Sp1, NF-Y, NF-1, Myb, AP-1 and E2F transcription factors. In this work, we further explored the role of these boxes on the regulation of the Sp3 gene. Gel-shift and competition assays showed specific binding of NF-1, Myb, AP-1 and E2F. Furthermore, chromatin immunoprecipitation assays demonstrated that Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb, c-Jun and E2F1 actually occupied the Sp3 promoter in HeLa cells. Transient transfections and luciferase assays revealed activation of the Sp3 proximal promoter upon overexpression of NF-1, c-Myb, B-Myb, c-Jun and c-Fos, and repression after overexpression of E2F/DP1. Point mutation of the binding sites for NF1, Myb, AP1 and E2F and cell incubation with specific siRNAs further confirmed the role of these transcription factors in the regulation of the Sp3 promoter. The regulation of the endogenous Sp3 gene was also observed at the mRNA level when the studied transcription factors were overexpressed or knocked down by siRNA incubation. These results help to explain the complex regulation of the Sp3 gene, which depends, at least in part, on the relative amount of Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb, AP-1, and E2F proteins in the cell.
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PMID:Transcriptional regulation of the 5'-flanking region of the human transcription factor Sp3 gene by NF-1, c-Myb, B-Myb, AP-1 and E2F. 1834 22