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)

The alpha subunit gene encodes a common subunit shared by all glycoprotein hormones. This single copy gene is expressed in pituitary gonadotropes and thyrotropes of all mammals and in placental trophoblasts of primates and horses. Tandem cAMP response elements (CREs) in the promoter of the human gene are key mediators of this pattern of cell-specific expression. Replacing the palindromic CREs with non-primate variant CREs significantly attenuated activity in trophoblasts but not in gonadotropes. Furthermore, proteins binding the palindromic CRE cross-reacted with antibodies for CREB, CREM, ATF1, ATF2, and c-Jun, while proteins binding the variant CRE cross-reacted only with ATF2 and c-Jun antibodies. The data suggest that ATF2 and c-Jun can activate transcription through the CREs in gonadotropes but not in trophoblasts. Additional analyses indicated that while promoters with either palindromic or variant CREs have similar overall activity in gonadotropes, the variant CREs make a much smaller contribution to promoter activity than their palindromic counterparts. The weaker contribution of the variant CREs is compensated by the activity of two upstream elements present in the promoter. This compensation probably occurs through an indirect mechanism, as the binding affinity of proteins to the CRE is not influenced by the presence of these upstream elements.
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PMID:The cAMP response elements of the alpha subunit gene bind similar proteins in trophoblasts and gonadotropes but have distinct functional sequence requirements. 894 Jan 85

The transcription factor PU.1 is necessary for the development of multiple hematopoietic lineages and contributes to the activity of the immunoglobulin kappa 3' enhancer. A variety of proteins bind to the 3' enhancer (PU.1, PIP, ATF1, CREM, c-Fos, c-Jun, and E2A), but the mechanism of 3'-enhancer activity and the proteins necessary for its activity are presently unclear. We show here that PU.1 participates with other transcription factors in forming a higher-order complex with 3'-enhancer DNA sequences. Each protein is necessary for formation of this complex. Individually, transcription factors that bind to the 3' enhancer do not appreciably stimulate transcription in a cell type in which the 3' enhancer is normally silent (NIH 3T3). However, mixture of multiple transcription factors (PU.1, PIP, c-Fos, and c-Jun) can greatly activate the enhancer. PU.1 is necessary for maximal enhancer activity, but mutants of PU.1 that lack the transcriptional activation domain are nearly as efficient at stimulating enhancer activity as the wild-type PU.1 protein. PU.1 apparently can activate transcription by playing an architectural role in interactions with other transcription factors.
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PMID:PU.1 can participate in an active enhancer complex without its transcriptional activation domain. 899 Jan 72

This article reviews findings up to the end of 1997 about the inducible transcription factors (ITFs) c-Jun, JunB, JunD, c-Fos, FosB, Fra-1, Fra-2, Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif268); and the constitutive transcription factors (CTFs) CREB, CREM, ATF-2 and SRF as they pertain to gene expression in the mammalian nervous system. In the first part we consider basic facts about the expression and activity of these transcription factors: the organization of the encoding genes and their promoters, the second messenger cascades converging on their regulatory promoter sites, the control of their transcription, the binding to dimeric partners and to specific DNA sequences, their trans-activation potential, and their posttranslational modifications. In the second part we describe the expression and possible roles of these transcription factors in neural tissue: in the quiescent brain, during pre- and postnatal development, following sensory stimulation, nerve transection (axotomy), neurodegeneration and apoptosis, hypoxia-ischemia, generalized and limbic seizures, long-term potentiation and learning, drug dependence and withdrawal, and following stimulation by neurotransmitters, hormones and neurotrophins. We also describe their expression and possible roles in glial cells. Finally, we discuss the relevance of their expression for nervous system functioning under normal and patho-physiological conditions.
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PMID:Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. 985 69

Anergic T cells display a marked decrease in their ability to produce IL-2 even in the presence of optimal TCR and costimulatory signals. Using IL-2 enhancer/promoter-driven reporter constructs, we have previously identified a region that appears to be a target for cis transcriptional repression in anergy. This region of the promoter, which shares partial homology with a consensus AP-1-binding sequence, is located about -180 bp from the transcriptional start site. In the present study, we demonstrate that cAMP response element-binding protein/cAMP response element modulator (CREB/CREM), activating transcription factor-2/c-Jun, and Jun-Jun/Oct complexes bind to this site. However, the induction of anergy by prolonged stimulation through the TCR led to an increase in binding of only the CREB/CREM complex. Furthermore, the level of binding of this complex appeared to be up-regulated in both resting and restimulated anergic T cells. Finally, an IL-2 promoter-driven reporter construct that contained a mutation that specifically reduced the binding of the CREB/CREM complex displayed a decreased ability to be affected by anergy, while a construct that contained a mutation that decreased the binding of the Jun-Jun/Oct complex was still susceptible to anergy. These findings suggest that the -180 region of the IL-2 promoter is the target of a CREB/CREM transcriptional inhibitor that contributes to the repression of IL-2 production in T cell anergy.
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PMID:The -180 site of the IL-2 promoter is the target of CREB/CREM binding in T cell anergy. 1058 58

Secalonic acid D (SAD), a mycotoxin produced by Penicillium oxalicum in corn, induces cleft palate (CP) in the offspring of exposed dams. Results of recent studies suggest that protein kinase C (PKC) inhibition by SAD may be relevant to its CP-induction. Downstream effects of PKC are determined by the nature of transcription factors (TF) that form the activator protein-1 (AP-1) and the binding of AP-1 (and other TF) to the phorbol 12-O-tetradecanoate-13 acetate-response element (TRE) to form AP-1-TRE complex, neither of which have been studied in the palate. The aims of the present study were to identify the components of the murine palatal AP-1-TRE complex during development and to uncover the effects of SAD on this complex. Western blots and gel mobility shift assays of control palatal nuclear extracts revealed that, although all relevant TF are present in the palate throughout development, only cyclic-AMP response element (CRE) binding protein (CREB) and CRE-modulator protein-1 (CREM-1) and activating transcription factor-1 bound to TRE on Gestation Day (GD) 12. The pattern shifted to c-Jun and c-Fos (known AP-1 components) on GD 13 and 14. In SAD-treated offspring, however, CREM-1 alone; c-Jun, c-Fos, and CREB; and c-Jun and c-Fos bound to TRE on GD 12, 13, and 14, respectively. Binding of TF to TRE was inhibited by SAD on both GD 12 and 13. These results suggest that a dynamic shift in the binding of TF to TRE from PKA- to PKC-responsive TF occurs during palate development and that teratogens such as SAD can alter both the nature and extent of TF binding to TRE.
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PMID:Secalonic acid D alters the nature of and inhibits the binding of the transcription factors to the phorbol 12-O-tetradecanoate-13 acetate-response element in the developing murine secondary palate. 1109 66

Surfactant protein B (SP-B) is required for the maintenance of biophysical properties and physiological function of pulmonary surfactant. SP-B is expressed in a cell/tissue-specific manner by the alveolar type II and bronchiolar (Clara) epithelial cells of the lung and is developmentally and hormonally regulated. We previously identified a minimal promoter region containing -236/+39 base pairs (bp) of rabbit SP-B gene that is necessary and sufficient for high level promoter activity in NCI-H441 cells, a cell line with characteristics of Clara cells. In this study, we have characterized the functional importance of a novel DNA regulatory element, termed SP-B CRE, with the sequence TGAGGTCA in the SP-B minimal promoter. The SP-B CRE sequence shared homology to cyclic AMP responsive element (CRE) binding sequence and contained an overlapping nuclear receptor element binding half-site. Mutation of SP-B CRE into a scrambled sequence reduced promoter activity by greater than 70%, whereas mutation into a palindromic consensus CRE increased the promoter activity by 100%. Electrophoretic mobility shift assay (EMSA) and Western immunoblot analysis of affinity purified proteins interacting with SP-B CRE showed that it is a target for binding of members of the activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB) family of transcription factors, such as CREB, CREM, ATF-1, ATF-2 as well as c-Jun and TTF-1. Overexpression of CREB, ATF-2 and c-Jun inhibited SP-B promoter activity in NCI-H441 cells. These data have shown that members of the ATF/CREB family of transcription factors and c-Jun play important roles in mediating the transcriptional regulation of the SP-B gene.
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PMID:Identification of a novel DNA regulatory element in the rabbit surfactant protein B (SP-B) promoter that is a target for ATF/CREB and AP-1 transcription factors. 1136 10