Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P51532 (transcriptional activator)
6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pneumonitis followed by lung fibrosis is a frequent complication of radiation therapy of chest tumors. A hallmark of these fibrotic lesions is the excessive production and accumulation of extracellular matrix proteins such as type I collagen. In addition to TGF-beta1, IL-4 has been recognized as a potent inducer of collagen gene synthesis in fibroblasts. In this study, we analyzed the regulation of the alpha1(I) procollagen (COL1A1) promoter and the alpha2(I) procollagen (COL1A2) promoter by IL-4 in normal human lung fibroblasts. We provide evidence that the IL-4-induced transcriptional activator STAT6 binds to various sequences within the COL1A1 and COL1A2 promoter. The regulatory function of these regions was tested by reporter gene analysis using 5' deletions of the COL1A1 and COL1A2 promoter fused to the luciferase gene. Interleukin-4 treatment of human fibroblasts transiently transfected with COL1A1 promoter deletion constructs resulted in luciferase activity exceeding that of untreated fibroblasts by 25%, while luciferase activity driven by the COL1A2 promoter was enhanced by about 70% upon IL-4 treatment. A combined action of SP1, NFkappaB, and STAT6 essentially contributes to the IL-4 mediated COL1A2 gene activation. An AP2 site adjacent to the reverse orientated STAT6 consensus motif TTC N(3/4) GCT is located within 205 bases from the transcription start site and seems to support the moderate IL-4-induced COL1A1 gene activation. Interferon-gamma downregulation of transcription is mainly seen with the COL1A1 promoter.
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PMID:Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin-4: analysis of the functional collagen promoter sequences. 1460 27

Arabidopsis ZIM is a putative transcription factor containing an atypical GATA-type zinc-finger motif. Transcriptional activation by ZIM was tested using a transient GAL4 fusion assay and measuring the expression of a luciferase reporter in tobacco BY-2 cells. ZIM functioned as a transcriptional activator, and the transactivation domain was found to occur in its N-terminal acidic region.
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PMID:Arabidopsis ZIM, a plant-specific GATA factor, can function as a transcriptional activator. 1464 19

There is evidence that 8q amplification is associated with poor prognosis in hepatoblastoma. A previous comparative genomic hybridization analysis identified a critical region in chromosomal bands 8q11.2-q13. Using restriction landmark genomic scanning in combination with a virtual genome scan, we showed that this region is delineated by sequences within contig NT_008183 of chromosomal subbands 8q11.22-q11.23. A real-time PCR-based genomic copy number assay of 20 hepatoblastomas revealed gain or amplification in this critical chromosomal region in eight tumors. The expression of four genes and expressed sequence tags (ESTs) within this newly defined region was assayed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in four tumors with and six tumors without gain or amplification. The PLAG1 oncogene was found to be highly expressed in all but one tumor compared to normal liver tissue. Furthermore, quantitative RT-PCR revealed that the expression level of the developmentally regulated transcription factor PLAG1 was 3-12 times greater in hepatoblastoma tumors and cell lines compared to age-matched normal liver and comparable to the expression in fetal liver tissue. PLAG1 has been shown be a transcriptional activator of IGF2 in other tumor types. Using luciferase reporter assays, we demonstrated that PLAG1 transactivates transcription from the embryonic IGF2 promoter P3, also in hepatoblastoma cell lines. Thus, our results provide evidence that PLAG1 overexpression may be responsible for the frequently observed up-regulation of IGF2 in hepatoblastoma and therefore may be implicated in the molecular pathogenesis of this childhood neoplasia.
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PMID:Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. 1469 92

The transcription factors MyoD and Myf-5 control myoblast identity and differentiation. MyoD and Myf-5 manifest opposite cell cycle-specific expression patterns. Here, we provide evidence that MyoD plays a pivotal role at the G(2)/M transition by controlling the expression of p21(Waf1/Cip1) (p21), which is believed to regulate cyclin B-Cdc2 kinase activity in G(2). In growing myoblasts, MyoD reaccumulates during G(2) concomitantly with p21 before entry into mitosis; MyoD is phosphorylated on Ser5 and Ser200 by cyclin B-Cdc2, resulting in a decrease of its stability and down-regulation of both MyoD and p21. Inducible expression of a nonphosphorylable MyoD A5/A200 enhances the MyoD interaction with the coactivator P/CAF, thereby stimulating the transcriptional activation of a luciferase reporter gene placed under the control of the p21 promoter. MyoD A5/A200 causes sustained p21 expression, which inhibits cyclin B-Cdc2 kinase activity in G(2) and delays M-phase entry. This G(2) arrest is not observed in p21(-/-) cells. These results show that in cycling cells MyoD functions as a transcriptional activator of p21 and that MyoD phosphorylation is required for G(2)/M transition.
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PMID:Mutant MyoD lacking Cdc2 phosphorylation sites delays M-phase entry. 1474 95

Nrf-2 is a redox-sensitive transcription factor that is activated by an oxidative signal in the cytoplasm but has a critical cysteine that must be reduced to bind to DNA in the nucleus. The glutathione (GSH) and thioredoxin (TRX) systems have overlapping functions in thiol/disulfide redox control in both the cytoplasm and the nucleus, and it is unclear whether these are redundant or have unique functions in control of Nrf-2-dependent signaling. To test whether GSH and Trx-1 have distinct functions in Nrf-2 signaling, we selectively modified GSH by metabolic manipulation and selectively modified Trx-1 expression by transient transfection. Cytoplasmic activation of Nrf-2 was measured by its nuclear translocation and nuclear activity of Nrf-2 was measured by expression of a luciferase reporter construct containing an ARE4 from glutamate cysteine ligase. Results showed that tert-butylhydroquinone (TBHQ), a transcriptional activator that functions through Nrf-2/ARE, promoted Nrf-2 nuclear translocation by a type I (thiylation) redox switch which was regulated by GSH not by Trx-1. In contrast, the ARE reporter was principally controlled by nuclear-targeted Trx-1 and not by GSH. The data show that the GSH and TRX systems have unique, compartmented functions in the control of transcriptional regulation by Nrf-2/ARE.
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PMID:Compartmentation of Nrf-2 redox control: regulation of cytoplasmic activation by glutathione and DNA binding by thioredoxin-1. 1567 96

Mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) is an essential component of the glycerol phosphate shuttle that transfers reduction equivalents from the cytosol into the mitochondrion. Within the testis, immunohistological analysis localized human mGPDH to late spermatids and to the midpiece of spermatozoa. The expression of human mGPDH is regulated by two somatic promoters, and here, we describe a third testis-specific promoter of human mGPDH. The usage of this testis-specific promoter correlates with the expression of a shortened mGPDH transcript of approximately 2.4 kb in length, which is solely detectable from testicular RNA. Within the testis-specific promoter, we detected a cAMP-response element (CRE) site at -51, which binds the testis-specific transcriptional activator CRE modulator tau (CREMtau) in electrophoretic mobility shift assays. This recognition site overlaps with a nuclear receptor binding half-site at -49, which binds the testis-specific transcriptional repressor germ cell nuclear factor (GCNF). Both factors compete for binding to the same DNA response element. Ectopic expression of CREMtau in HepG2 cells activated a promoter-driven luciferase construct in transient transfection experiments. Additional cotransfection of GCNF relieved this activity, suggesting a down-regulation of CREMtau-mediated activation by GCNF. This effect was preserved by introducing the CRE/nuclear receptor-binding element into a heterologous promoter context. Our data suggest a down-regulation of CREMtau-mediated gene expression by GCNF, which might be a general regulation mechanism for several postmeiotically expressed genes with a temporal expression peak during early spermatid development.
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PMID:Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated activation of the testis-specific promoter of human mitochondrial glycerol-3-phosphate dehydrogenase. 1545 63

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in adaptation to hypoxic stress. Previous studies from our laboratory demonstrated that pharmacological activators of HIF-1 (e.g. deferoxamine, cobalt chloride) could also protect cultured primary neurons or an immortalized hippocampal neuroblast line (HT22) from oxidative stress-induced death. However, whether HIF-1 activation is sufficient to abrogate neuronal death resulting from oxidative stress or other hypoxia-independent death inducers remains unclear. To address this question we utilized a HIF-1alpha fusion protein that partially lacks the domain required for oxygen-dependent degradation of HIF-1alpha and that has a VP16 transcriptional activation domain from herpes simplex virus. HT22 cells were infected with a retrovirus encoding either the HIF-1alpha-VP16 fusion protein or the activation domain of the VP16 protein alone as a control. Expression of HIF-1alpha-VP16, but not VP16 alone, increased luciferase activity driven by a canonical hypoxia response element, increased mRNA of established HIF-1 target genes, and increased activity of one of these HIF-1 target genes. Unexpectedly, enhanced HIF-1 activity in HT22 cells enhanced sensitivity to oxidative death induced by glutathione depletion. Accordingly, suppression of HIF-1alpha expression using RNA interference prevented oxidative death. By contrast, HIF-1alpha-VP16-expressing HT22 cells were more resistant to DNA damage (induced by camptothecin) or endoplasmic reticulum stress (induced by thapsigargin and tunicamycin) than were VP16-expressing cells, and suppression of HIF-1alpha expression using RNA interference rendered HT22 cells more sensitive to death induced by DNA damage or endoplasmic reticulum stress. Together, these data demonstrate that HIF-1 can mediate prodeath or prosurvival responses in the same cell type depending on the injury stimulus.
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PMID:Prosurvival and prodeath effects of hypoxia-inducible factor-1alpha stabilization in a murine hippocampal cell line. 1555 37

Hypothalamic GnRH is a decapeptide that plays a pivotal role in mammalian reproduction by stimulating the synthesis and secretion of gonadotropins via binding to the GnRH receptor on the pituitary gonadotropins. It is hypothesized that sex steroids may regulate GnRH I (a classical form of GnRH), GnRH II (a second form of GnRH), and GnRH I receptor (GnRHRI) at the transcriptional level in target tissues. Thus, in the present study a role for progesterone (P4) in the regulation of GnRH I, GnRH II, and GnRHRI was investigated using a human neuronal medulloblastoma cell line (TE671) as an in vitro model. The cells were transfected with human GnRHRI promoter-luciferase constructs, and promoter activities were analyzed after P4 treatment by luciferase and beta-galactosidase assay. The mRNA levels of GnRH I and GnRH II were analyzed by RT-PCR. Treatment of TE671 cells with P4 resulted in a decrease in GnRHRI promoter activity compared with the control level in a dose- and time-dependent manner. Cotreatment of these cells with RU486, an antagonist of P4, reversed P4-induced inhibition of GnRHRI promoter activity, suggesting that the P4 effect is mediated by P4 receptor (PR). In the cells transfected with a full-length of PR A- or PR B-expressing vector, overexpression of PR A increased the sensitivity toward P4 in an inhibition of GnRHRI promoter, whereas PR B increased transcriptional activity of GnRHRI promoter in the presence of P4. However, PR B itself did not act as a transcriptional activator of GnRHRI promoter. Because TE671 cells have been recently demonstrated to express and synthesize two forms of GnRHs, we also investigated the regulation of GnRH mRNAs by P4. In the present study, P4 increased GnRH I mRNA levels in a time- and dose-dependent manner. This stimulatory effect of P4 in the regulation of GnRH I mRNAs was significantly attenuated by RU486, whereas no significant difference in the expression level of GnRH II was observed with P4 or RU496. Interestingly, although the expression level of PR B was low compared with that of PR A, P4 action on the GnRH I gene was mediated by PR B. In conclusion, these results indicate that P4 is a potent regulator of GnRHRI at the transcriptional level as well as GnRH I mRNA. This distinct effect of P4 on the GnRH system may be derived from different pathways through PR A or PR B.
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PMID:Differential role of progesterone receptor isoforms in the transcriptional regulation of human gonadotropin-releasing hormone I (GnRH I) receptor, GnRH I, and GnRH II. 1556 29

We isolated an enhancer activation-tagged mutant of Arabidopsis thaliana line sGsL carrying the luciferase (LUC) gene under control of a short sugar-inducible promoter derived from a sweet potato sporamin gene (Spomin) that showed high level expression of LUC under non-inducing conditions. The activator of Spomin::LUC1 (ASML1) gene located downstream of the enhancer encoded an APETALA2 (AP2)-type AP2 domain protein, and this gene was shown recently to be responsible for the wrinkled1 mutation which causes defective accumulation of seed storage oil. Overexpression of ASML1 cDNA in sGsL plants resulted in enhanced expression of not only the LUC reporter but also endogenous sugar-inducible genes including Atbeta-Amy encoding beta-amylase. Transient co-expression of 35S::ASML1 with Spomin::LUC or Atbeta-Amy::LUC reporters in protoplasts resulted in an approximately 10-fold transactivation of LUC expression. This transactivation was lost when the C-terminal acidic region of ASML1 was deleted. Expression of ASML1 was high in reproductive organs, and ASML1 mRNA showed transient accumulation in leaves after treatment with 6% sucrose, whereas it did not respond to abscisic acid. These results suggest that ASML1/WRI1 is a transcriptional activator involved in the activation of a subset of sugar-responsive genes and the control of carbon flow from sucrose import to oil accumulation in developing seeds.
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PMID:ACTIVATOR of Spomin::LUC1/WRINKLED1 of Arabidopsis thaliana transactivates sugar-inducible promoters. 1575 6

NF45/ILF2 associates with NF90/ILF3 in the nucleus and regulates IL-2 gene transcription at the antigen receptor response element (ARRE)/NF-AT DNA target sequence (P.N. Kao, L. Chen, G. Brock, J. Ng, A.J. Smith, B. Corthesy, J. Biol. Chem. 269 (1994) 20691-20699). NF45 is widely expressed in normal tissues, especially testis, brain, and kidney, with a predominantly nuclear distribution. NF45 mRNA expression is increased in lymphoma and leukemia cell lines. The human and murine NF45 proteins differ only by substitution of valine by isoleucine at amino acid 142. Fluorescence in situ hybridization localized the human NF45 gene to chromosome 1q21.3, and mouse NF45 gene to chromosome 3F1. Promoter analysis of 2.5 kB of the murine NF45 gene reveals that significant activation is conferred by factors, possible including NF-Y, that bind to the CCAAT-box sequence. The function of human NF45 in regulating IL-2 gene expression was characterized in Jurkat T-cells stably transfected with plasmids directing expression of NF45 cDNA in sense or antisense orientations. NF45 sense expression increased IL-2 luciferase reporter gene activity 120-fold, and IL-2 protein expression 2-fold compared to control cells. NF45 is a highly conserved, regulated transcriptional activator, and one target gene is IL-2.
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PMID:NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function. 1581 56


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