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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane depolarization, or agents which increase intracellular calcium, elicit transcriptional activation of tyrosine hydroxylase (TH). In this study we analyze the factors involved in the regulation of the TH promoter by a calcium ionophore. PC12 cells were transiently transfected with plasmids containing wild type or mutated 5' flanking sequences of the rat TH gene, fused to bacterial chloramphenicol acetyl transferase (CAT). Point mutations introduced into the consensus cAMP-regulatory element (CRE) abolished the induction of CAT by ionomycin indicating that it is essential for mediating the calcium response. An intact and functional AP1 site did not confer calcium inducibility when the CRE/CaRE sequence was mutated. The extent and kinetics of the increase in intracellular calcium as well as the induction of CAT activity under the control of TH promoter by ionomycin were similar in PC12 cells and in the A123.7, protein kinase A (PKA) deficient cell line. In both cell lines addition of ionomycin rapidly increased the phosphorylation of transcription factor CREB at Ser-133. These results suggest that the activation of TH transcription by ionomycin does not require PKA. However, KN62 an inhibitor of Ca2+/calmodulin dependent (CaM) kinases prevented the induction indicating possible involvement of CAM kinases in the calcium response.
Brain Res Mol Brain Res 1996 Jan
PMID:Promoter elements and second messenger pathways involved in transcriptional activation of tyrosine hydroxylase by ionomycin. 871 52

A potato MADS-box gene cDNA (POTM1-1) from an early tuber cDNA library has been isolated and characterized. The deduced amino acid sequence of POTM1-1 cDNA encodes 250 amino acids of a putative transcription factor containing a MADS-box domain and a K-box domain. These conserved domains share high homologies to those of flower-specific homeotic proteins, TM4 of tomato and AP1 of Arabidopsis, indicating that POTM1-1 gene is a homologue of the AP1 gene family. The levels of POTM1-1 transcripts were high in axillary buds, underground stolen tips, and newly formed tubers, but relatively low in mature tubers. During axillary bud development in a model petiole-leaf cutting system, the levels of POTM1-1 transcripts were abundant in actively growing shoots and during the early stages of microtuber development. It is possible that POTM1-1 functions as a transcription factor that regulates plant developmental processes in a number of tissue types.
Plant Mol Biol 1996 May
PMID:A novel MADS-box gene of potato (Solanum tuberosum L.) expressed during the early stages of tuberization. 875 1

Our group has previously reported that the nuclear factor Yin-Yang 1 (YY1), a ubiquitous DNA-binding protein, is able to interact with a silencer element (BE) in the gamma interferon (IFN-gamma) promoter region. In this study, we demonstrated that YY1 can directly inhibit the activity of the IFN-gamma promoter by interacting with multiple sites in the promoter. In cotransfection assays, a YY1 expression vector significantly inhibited IFN-gamma promoter activity. Mutation of the YY1 binding site in the native IFN-gamma promoter was associated with an increase in the IFN-gamma promoter activity. Analysis of the DNA sequences of the IFN-gamma promoter revealed a second functional YY1 binding site (BED) that overlaps with an AP1 binding site. In this element, AP1 enhancer activity was suppressed by YY1. Since the nuclear level of YY1 does not change upon cell activation, our data support a model that the nuclear factor YY1 acts to suppress basal IFN-gamma transcription by interacting with the promoter at multiple DNA binding sites. This repression can occur through two mechanisms: (i) cooperation with an as-yet-unidentified AP2-like repressor protein and (ii) competition for DNA binding with the transactivating factor AP1.
Mol Cell Biol 1996 Sep
PMID:The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silencer element. 875 32

AP1 is a heterodimeric complex containing products of the Jun and Fos oncogene families. The c-fos and c-jun protooncogenes act as transcriptional activator for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. In this study, to show evidence of a possible inhibition of AP1 transcriptional activity in molecular mechanisms of foodborne molecules, known to be negative modulators of carcinogenesis, we established two rat liver epithelial (REL) cell lines overexpressing either c-fos (43C line) or c-jun (RELcJ1 line) oncoproteins. Contrary to the 43C line, which was spontaneously transformed, the c-jun-transfected REL cells were only transformed in vitro after 12-O-tetra-decanoylphorbol 13-acetate (TPA) exposure. All trans-retinoic acid (RA) abolished the transformation of the 43C line and TPA-treated RELcJ1 cells, suggesting that RA could decrease AP1 activity in these cells despite c-fos or c-jun overexpression. Furthermore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation of the 43C line. The spontaneous transformation of the c-fos-transfected REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the antitransforming mechanism of quercetin.
Cell Mol Biol Res 1995
PMID:Suppression of oncogene-induced transformation by quercetin and retinoic acid in rat liver epithelial cells. 877 34

In the corticotroph cell line AtT20, Ca2+ stimulates c-fos mRNA and nuclear c-fos protein accumulation. We show that Ca2+ stimulates transcription of a chloramphenicol-acetyl-transferase reporter gene driven by the c-fos promoter. This effect is mimicked by both constitutively active Ca2+/calmodulin-dependent protein kinase types II (CamK II) and IV (CamK IV). The effects of CamK IV are synergistic with those obtained by cAMP stimulation, whereas CamK II-dependent transcription is not further stimulated. Deletion of the distal promoter sequence revealed that CamK IV, and to a lesser extent CamK II, activate a cis-acting element(s) located between -99 and -53 bp prior to the transcription initiation site. Moreover, CamK II further stimulates transcription through the fos AP1-like element. CamK IV has a lower effect on this element but represses the serum response element. The latter observation might account for the lower transcriptional effects of CamK IV on the full length c-fos promoter.
Mol Cell Endocrinol 1996 Jun 18
PMID:Ca2+/calmodulin kinase types II and IV regulate c-fos transcription in the AtT20 corticotroph cell line. 880 32

The human beta-globin locus control region (LCR) is responsible for forming an active chromatin structure extending over the 100-kb locus, allowing expression of the beta-globin gene family. The LCR consists of four erythroid-cell-specific DNase I hypersensitive sites (HS1 to -4). DNase I hypersensitive sites are thought to represent nucleosome-free regions of DNA which are bound by trans-acting factors. Of the four hypersensitive sites only HS2 acts as a transcriptional enhancer. In this study, we examine the binding of an erythroid protein to its site within HS2 in chromatin in vitro. NF-E2 is a transcriptional activator consisting of two subunits, the hematopoietic cell-specific p45 and the ubiquitous DNA-binding subunit, p18. NF-E2 binds two tandem AP1-like sites in HS2 which form the core of its enhancer activity. In this study, we show that when bound to in vitro-reconstituted chromatin, NF-E2 forms a DNase I hypersensitive site at HS2 similar to the site observed in vivo. Moreover, NF-E2 binding in vitro results in a disruption of nucleosome structure which can be detected 200 bp away. Although NF-E2 can disrupt nucleosomes when added to preformed chromatin, the disruption is more pronounced when NF-E2 is added to DNA prior to chromatin assembly. Interestingly, the hematopoietic cell-specific subunit, p45, is necessary for binding to chromatin but not to naked DNA. Interaction of NF-E2 with its site in chromatin-reconstituted HS2 allows a second erythroid factor, GATA-1, to bind its nearby sites. Lastly, nucleosome disruption by NF-E2 is an ATP-dependent process, suggesting the involvement of energy-dependent nucleosome remodeling factors.
Mol Cell Biol 1996 Oct
PMID:NF-E2 disrupts chromatin structure at human beta-globin locus control region hypersensitive site 2 in vitro. 881 76

Tyrosine hydroxylase (TH) gene transcription rate is increased in rat adrenal medulla after administration of muscarinic agonists. In order to study this muscarinic regulation of TH gene expression in more detail, we have generated a rat pheochromocytoma PC18 cell line that stably expresses the mouse m1 muscarinic acetylcholine receptor. Treatment of this cell line, designated PC18/m1-13, with carbachol leads to rapid increases in phosphatidylinositol turnover and intracellular [Ca2+]i; these increases are totally blocked by the muscarinic antagonist atropine. Carbachol produces no changes in cAMP levels or protein kinase A activity in PC18/m1-13 cells. TH mRNA levels in PC18/m1-13 cells increase approximately 3-fold after 6 h of treatment with carbachol. This induction of TH mRNA is also completely inhibited by simultaneous treatment with atropine. Transient transfection assays using a TH gene promoter-chloramphenicol acetyltransferase (TH-CAT) construct demonstrate that sequences within the most proximal 272 bp of the TH gene 5'-flanking region are responsive to carbachol in PC18/m1-13 cells. Studies using TH-CAT constructs with site-directed mutations within the TH gene promoter indicate that the responsiveness of the promoter to carbachol is mediated primarily by the cAMP response element; however, the AP1 site also participates to a lesser extent in this response. The carbachol-mediated stimulation of TH gene promoter activity is partially inhibited by down-regulation of protein kinase C (PKC) or by treatment with the Ca2+/calmodulin-dependent protein kinase inhibitor, KN62. These results are consistent with the hypothesis that agonist occupation of m1 muscarinic receptors stimulates the TH gene via signal transduction pathways that are initiated by activation of PKC and Ca2+/calmodulin-dependent protein kinase, leading to activation of transcription factors that interact with the TH CRE and AP1 sites.
Brain Res Mol Brain Res 1996 Aug
PMID:Regulation of tyrosine hydroxylase gene expression by the m1 muscarinic acetylcholine receptor in rat pheochromocytoma cells. 884 12

The structure and expression of a clone containing the promoter region, all of exon 1, and part of the first intron of the human mineralocorticoid receptor (hMR) gene is presented. The clone has three sets of CAAT and TATA elements, one located at the very 5'-end of the clone, one located just 5'- to the start of transcription, and one set located in intron A, approximately 300 bp into the intron. The major start of transcription site by primer extension analysis and ribonuclease protection assays is located 26 bp downstream of a TATA-like box (TTTAA) and 90 and 143 bp downstream, respectively, of two CCAAT boxes. Putative cis-transcription factor binding sites are as follows: two potential AP1 sites, one potential AP2 site, two ATF/CREB sites, six potential GC boxes or SP1 sites, one potential perfect half-palindromic estrogen response element, and three potential PEA3 sites. Therefore, the hMR promoter region contains elements characteristic of both regulated genes and "housekeeping" genes. CAT assays of overlapping deletions of the promoter region demonstrated tissue-specific regulation in human neuroepithelioma (SK-N-MC-IXC) and non-neuronal, peripheral choriocarcinoma cell lines (JEG-3).
J Steroid Biochem Mol Biol 1996 Aug
PMID:The human mineralocorticoid receptor gene promoter: its structure and expression. 891 75

Research in our laboratory is aimed at understanding the cellular and molecular mechanisms that govern colony stimulating factor-1 (CSF-1) gene expression. Our hypothesis is that a basal set of trans-acting factors is bound to the CSF-1 gene during fibroblast proliferation, resulting in constitutive CSF-1 gene expression. Modulation of CSF-1 gene transcription by growth-arrest (decrease) or stimulation of growth-arrested fibroblasts (re-initiate) is mediated by changes in the basal set of factors bound and/or by the addition of stimulus-specific factors. We have extended our hypothesis to include other cell types (monocytes) to determine if mechanisms used to control CSF-1 gene expression in fibroblasts are unique or represent common nontissue-specific regulatory mechanisms. Analysis of CSF-1-CAT reporter constructs in transiently transfected fibroblasts and monocytes was used to identify CSF-1 genomic sequences that affect transcriptional activity. DNase I protection, electrophoretic mobility shift, and methylation interference assays were used to identify the putative cis-acting elements. Results of our study suggest multiple trans-acting factors may regulate CSF-1 gene expression; some may be tissue specific, while others, such as AP1, CTF/NF1, Sp1, and Sp3, are shared in common.
Mol Reprod Dev 1997 Jan
PMID:Transcriptional regulation of the mouse CSF-1 gene. 898 62

The epidermis is a tissue that undergoes a very complex and tightly controlled differentiation program. The elaboration of this program is generally flawless, resulting in the production of an effective protective barrier for the organism. Many of the genes expressed during keratinocyte differentiation are expressed in a coordinate manner; this suggests that common regulatory models may emerge. The simplest model envisions a 'common regulatory element' that is possessed by all genes that are regulated together (e.g., involucrin and transglutaminase type 1). Studies to date, however, have not identified any such elements and, if anything, the available studies suggest that appropriate expression of each gene is achieved using sometime subtly and sometime grossly different mechanisms. Recent studies indicate that a variety of transcription factors (AP1, AP2, POU domain. Sp1, STAT factors) are expressed in the epidermis and, in many cases, multiple members of several families are present (e.g., AP1 and POU domain factors). The simultaneous expression of multiple members of a single transcription factor family provides numerous opportunities for complex regulation. Some studies suggest that specific members of these families interact with specific keratinocyte genes. The best studied of these families in epidermis is the AP1 family of factors. All of the known AP1 factors are expressed in epidermis [52] and each is expressed in a specific spatial pattern that suggests the potential to regulate multiple genes. It will be important to determine the role of each of these members in regulating keratinocyte gene expression. Finally, information is beginning to emerge regarding signal transduction in keratinocytes. Some of the early events in signal transduction have been identified (e.g., PLC and PKC activation, etc.) and some of the molecular targets of these pathways (e.g., AP1 transcription factors) are beginning to be identified. Eventually we can expect to elucidation of all of the steps between the interaction of the stimulating agent with its receptor and the activation of target gene expression.
Mol Biol Rep 1996
PMID:Transcription factor regulation of epidermal keratinocyte gene expression. 898 19


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