Showing papers on "Transcription factor published in 1988"
TL;DR: The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor in cells that do not express immunoglobulin kappa light chain genes.
Abstract: In cells that do not express immunoglobulin kappa light chain genes, the kappa enhancer binding protein NF-kappa B is found in cytosolic fractions and exhibits DNA binding activity only in the presence of a dissociating agent such as sodium deoxycholate. The dependence on deoxycholate is shown to result from association of NF-kappa B with a 60- to 70-kilodalton inhibitory protein (I kappa B). The fractionated inhibitor can inactivate NF-kappa B from various sources--including the nuclei of phorbol ester-treated cells--in a specific, saturable, and reversible manner. The cytoplasmic localization of the complex of NF-kappa B and I kappa B was supported by enucleation experiments. An active phorbol ester must therefore, presumably by activation of protein kinase C, cause dissociation of a cytoplasmic complex of NF-kappa B and I kappa B by modifying I kappa B. this releases active NF-kappa B which can translocate into the nucleus to activate target enhancers. The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor.
2,071 citations
TL;DR: Drosophila tissue culture cells provide an Sp1-deficient background and have been used in a complementation assay to identify functional domains of human transcription factor Sp1, and it is proposed that these glutamine-rich domains represent a novel structural motif for transcriptional activation.
1,295 citations
TL;DR: Fos is a trans-acting factor that is capable of stimulating gene expression not by direct binding to DNA but by interaction with the sequence-specific transcription factor AP-1, therefore recognition of specific cis-elements by AP- 1 is a prerequisite for Fos-mediated stimulation of gene expression.
1,269 citations
TL;DR: In this paper, the human transcription factor Jun/AP-1 was found to be responsible for increased transcription of different cellular genes in response to tumor promoters, such as TPA, and serum factors.
1,095 citations
TL;DR: It is concluded that both 70Z/3 and HeLa cells contain apparently cytosolic NF-kappa B in a form with no evident DNA-binding activity, and phorbol esters both release the inhibition of binding and cause a translocation to the nucleus.
1,095 citations
TL;DR: Receptors for retinoic acid, vitamin D3 and the steroid and thyroid hormones belong to a family of ligand-activated enhancer-binding factors which are composed of a number of functional domains required for ligand and DNA binding, nuclear translocation, dimerization and trans -activation of transcription.
987 citations
TL;DR: The structure of Pit-1 and its recognition elements suggests that metazoan tissue phenotype is controlled by a family of transcription factors that bind to related cis-active elements and contain several highly conserved domains.
941 citations
TL;DR: A cDNA clone of SRF expressed in vitro generates protein that forms complexes indistinguishable from those formed with HeLa cell SRF, as judged by DNA binding specificity and the ability to promote SRE-dependent in vitro transcription.
862 citations
TL;DR: The putative DNA-binding domain of CREB is structurally similar to the corresponding domains in the phorbol ester-responsive c-jun protein and the yeast transcription factor GCN4.
Abstract: Cyclic AMP (cAMP) is an intracellular second messenger that activates transcription of many cellular genes. A palindromic consensus DNA sequence, TGACGTCA, functions as a cAMP-responsive transcriptional enhancer (CRE). The CRE binds a cellular protein of 38 kD in placental JEG-3 cells. A placental lambda gt11 library was screened for expression of specific CRE-binding proteins with the CRE sequence as a radioactive probe. A cDNA encoding a protein of 326 amino acids with the binding properties of a specific CRE-binding protein (CREB) was isolated. The protein contains a COOH-terminal basic region adjacent to a sequence similar to the "leucine zipper" sequence believed to be involved in DNA binding and in protein-protein contacts in several other DNA-associated transcriptional proteins including the products of the c-myc, c-fos, and c-jun oncogenes and GCN4. The CREB protein also contains an NH2-terminal acidic region proposed to be a potential transcriptional activation domain. The putative DNA-binding domain of CREB is structurally similar to the corresponding domains in the phorbol ester-responsive c-jun protein and the yeast transcription factor GCN4.
707 citations
TL;DR: Comparisons of cDNAs encoding potential finger proteins indicate the existence of at least two classes of proteins with specific nucleic acid recognition capabilities, characterized according to the number and position of the cysteine and histidine residues available for zinc coordination.
680 citations
TL;DR: It is suggested that this inhibition, which the authors call squelching, reflects titration of a transcription factor by the activating region of GAL4, and that more efficient activators inhibit more strongly and that inhibition does not depend on the DNA-binding domain.
Abstract: The yeast transcriptional activator GAL4 binds specific sites on DNA to activate transcription of adjacent genes. The distinct activating regions of GAL4 are rich in acidic residues and it has been suggested that these regions interact with another protein component of the transcriptional machinery (such as the TATA-binding protein or RNA polymerase II) while the DNA-binding region serves to position the activating region near the gene. Here we show that various GAL4 derivatives, when expressed at high levels in yeast, inhibit transcription of certain genes lacking GAL4 binding sites, that more efficient activators inhibit more strongly and that inhibition does not depend on the DNA-binding domain. We suggest that this inhibition, which we call squelching, reflects titration of a transcription factor by the activating region of GAL4.
TL;DR: It is now clear that many promoters, particularly those of 'housekeeping' genes, lack TATA boxes and are instead composed of GC-rich elements that are often located within methylation-free islands (Bird 1986).
Abstract: Our knowledge of the mechanisms that regulate transcription in higher eukaryotic cells has increased enormously during the past 2 years. Earlier studies, using a combination of in vitro mutagenesis and DNA-mediated gene transfer, identified two distinct types of cis-acting regulatory sequences: promoters, which are located close to the initiation site and act in a position-dependent fashion, and enhancers, which can be located far from the initiation site and act in a position- and orientation-independent fashion. Promoters can be subdivided into proximal elements, including the cap site itself and the TATA box, which is involved in fixing the site of initiation, and distal elements, which can be spread over several hundred base pairs. It is now clear that many promoters, particularly those of 'housekeeping' genes, lack TATA boxes and are instead composed of GC-rich elements that are often located within methylation-free islands (Bird 1986). Transcription controlled by this latter class of promoters often initiates at multiple sites. Many enhancer elements, for example, those of the immunoglobulin, insulin, and elastase genes, impose tissue-specific expression on adjacent promoters. These cis-acting elements operate by interacting with protein factors, many of which have now been identified by gel retardation and footprinting assays and some of which have been purified to homogeneity. In a few cases the corresponding genes have been cloned. In many of these studies well-characterized cis-acting elements of viruses, particularly of the DNA tumor viruses, have played a major role. At the recent ICRF-sponsored
TL;DR: The findings that the products of nuclear proto-oncogenes jun and erbA are transcriptional factors supports the notion of the role of the nuclear oncoproteins in the regulation of gene expression.
Abstract: The response of a cell to mitogens and differentiation agents involves the transcriptional induction of several cellular genes. Prominent among these so-called 'immediate early' or 'competence' genes are the nuclear oncogenes fos and mycl–7. Although the precise function of these early response genes in growth control is not understood, it is likely that many of them are involved in the transition from G0 to G1 in the cell cycle. The findings that the products of nuclear proto-oncogenes jun and erbA are transcriptional factors supports the notion of the role of the nuclear oncoproteins in the regulation of gene expression8–11. Recently, it has been reported that the FOS protein is associated in transcriptional complexes with the product of the jun oncogene, the transcription factor AP-1 (refs 12–15). As the fos gene is induced in response to mitogens during initiation of cell growth, we investigated whether expression of the nuclear transcription factor AP-1 is also inducible. We report that mouse c-jun gene transcription is rapidly induced by serum and phorbol-ester 12-o-tetradecanoyl phorbol 13-acetate (TPA). Furthermore, induction is transient and the mRNA is superinduced by inhibitors of protein synthesis.
TL;DR: Using DNA transfection, it is shown that TGF-beta stimulates the activity of the mouse alpha 2(l) collagen promoter 5- to 10-fold in mouse NIH 3T3 and rat osteosarcoma cells.
TL;DR: Results suggest that the hormone plays at least a dual role in chimeric receptors, and the hormone, or anti-hormone, is responsible for receptor "transformation" allowing the recognition of responsive DNA elements.
TL;DR: It is shown that there is a dramatic increase in the FSE2 binding complex when Fos levels are induced with serum, benzodiazepine, and nerve growth factor or are expressed from a v-fos gene, suggesting a functional relationship between Fos and AP-1.
TL;DR: Transfection of cDNA clones into Drosophila cells indicates that the AP-2 gene product can also activate gene expression in vivo in a DNA template-dependent manner and may be a transcription factor involved in the control of developmentally regulated gene expression.
Abstract: Human AP-2 is a sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to stimulate transcription of selected genes. Here, we report the isolation and characterization of a human cDNA clone containing the entire protein-coding region of AP-2. The deduced primary amino acid sequence of AP-2 does not contain a domain resembling any previously identified DNA binding motif. However, an interesting feature of the AP-2 protein is a clustered arrangement of proline and glutamine residues that have been found recently within the activation domains of other transcription factors. Expression of the AP-2 clone in bacteria yields a protein that binds to DNA and activates transcription in vitro in a comparable manner to native human AP-2. Transfection of cDNA clones into Drosophila cells indicates that the AP-2 gene product can also activate gene expression in vivo in a DNA template-dependent manner. Expression of endogenous AP-2 is repressed in a hepatoma cell line and stimulated following retinoic-acid-induced differentiation of a human teratocarcinoma cell line. This indicates that AP-2 may be a transcription factor involved in the control of developmentally regulated gene expression.
TL;DR: These properties suggest that Krox-20 andKrox-24 may encode transcription factors with identical DNA target sequences and that these factors may be involved in the modulation of cell proliferation and differentiation.
Abstract: We previously reported the identification of a mouse gene, Krox-20, encoding a protein with three "zinc fingers" (DNA-binding domains with coordinated zinc ions) whose expression is regulated during G0/G1 transition (cell-cycle reentry). We now have isolated cDNAs corresponding to a related gene, Krox-24. Krox-24 encodes a protein with zinc fingers nearly identical to those encoded by Krox-20 and similar to those of transcription factor Sp1. Similarity between Krox-20 and Krox-24 proteins also extends to several blocks of amino acid sequence located upstream of the finger region. Like Krox-20, Krox-24 is transiently activated in quiescent cells after treatment with fetal bovine serum or purified growth factors. The kinetics of activation are similar to those of the protooncogene c-fos. The induction does not require de novo protein synthesis, and cycloheximide treatment of the cells leads to superinduction due, at least in part, to mRNA stabilization. In the mouse, the two genes are expressed in a tissue-specific manner, with slightly different patterns. These properties suggest that Krox-20 and Krox-24 may encode transcription factors with identical DNA target sequences and that these factors may be involved in the modulation of cell proliferation and differentiation.
TL;DR: Evidence is found that a similar transcription factor is involved in the induction of IL-2Rα expression by tat-I, which interacts with NF-κB-like transcription factors which might normally regulate expression of a growth factor receptor gene.
Abstract: Like other viruses that infect primate cells, the human T lymphotropic virus-I (HTLV-I) stimulates production of some host cell proteins. In particular, HTLV-I infected T cells synthesize interleukin-2 receptor alpha (IL-2R alpha) chain, which is probably induced through the mediation of the tat-I gene product of the virus. Activated T cells contain a trascription factor called NF-kappa B, which stimulates the expression of human immunodeficiency virus-1 (HIV-1) by binding to an 11-base-pair enhancer sequence called kappa B. We have now found evidence that a similar transcription factor is involved in the induction of IL-2R alpha expression by tat-I. We have identified a sequence upstream of IL-2R alpha which is the same as the kappa B site at 9 of 11 base pairs, competes for binding to the kappa B sequence, and serves as a tat-I responsive element when multiple copies are inserted upstream of a heterologous promoter. The tat-I product also induces kappa B and the IL-2R alpha kappa B binding activity in transfected Jurkat T lymphoid leukaemia cells. Both HTLV-I and HIV-1 thus interact with NF-kappa B-like transcription factors which might normally regulate expression of a growth factor receptor gene.
TL;DR: It is reported here that a protein of relative molecular mass 19,000 encompassing the DNA-binding domain of the glucocorticoid receptor that has been overexpressed in Escherichia coli and purified to homogeneity reversibly ligates two Zn(II) or Cd( II) ions.
Abstract: The glucocorticoid receptor enhances or represses transcription by binding to specific DNA sequences termed glucocorticoid response elements, or GREs1–5. Studies of cloned glucocorticoid receptors6–8 reveal that the protein is organized as functional domains, in an arrangement that appears to be common among members of the steroid receptor family9. A segment near the centre of the gene specifies DNA binding activity in vitro and contains two sequence motifs similar to 'zinc fingers' found in Xenopus transcription factor III A (TFIIIA)10. Such sequence motifs have been identified in nucleic acid binding proteins from a wide range of organisms11–13. Steroid receptor protein fingers are proposed to bind zinc through two pairs of conserved cysteine residues7,14,15.We report here that a protein of relative molecular mass 19,000 (Mr = 19K) encompassing the DNA-binding domain of the glucocorticoid receptor that has been overexpressed in Escherichia coli and purified to homogeneity reversibly ligates two Zn(II) or Cd(II) ions. We show that metal ions are required for specific DNA binding and proper folding. Using EXAFS (extended X-ray absorption fine structure) and visible light spectroscopies, we find that each Zn atom is coordinated in a tetrahedral arrangement by four cysteines.
TL;DR: Results suggest that the growth factor-inducible immediate early gene nur/77 encodes a ligand-binding protein that regulates the genomic response to growth factors.
Abstract: We previously identified, by cDNA cloning, a set of genes that are expressed during the G0/G1 transition (cell cycle reentry) in mouse fibroblasts. These immediate early genes are transcriptionally activated within minutes of addition of serum or purified growth factors, and their mRNAs are superinduced in the presence of protein-synthesis inhibitors. We report here that one of these genes, represented by nur/77 cDNA (originally called 3CH77), encodes a member of the superfamily of ligand-binding transcription factors that includes the steroid and thyroid hormone receptors. The nur/77 cDNA sequence encodes a protein of 601 amino acids containing two regions of sequence similarity to members of this nuclear receptor superfamily, corresponding to their DNA-binding and ligand-binding domains. These results suggest that the growth factor-inducible immediate early gene nur/77 encodes a ligand-binding protein that regulates the genomic response to growth factors.
TL;DR: The data suggest that, in the course of development, a single tissue-specific factor activates sets of genes that ultimately exhibit restricted cell-specific expression and define cellular phenotype.
Abstract: In the anterior pituitary gland, there are five phenotypically distinct cell types, including cells that produce either prolactin (lactotrophs) or growth hormone (somatotrophs). Multiple, related cis-active elements that exhibit synergistic interactions appear to be the critical determinants of the transcriptional activation of the rat prolactin and growth hormone genes. A common positive tissue-specific transcription factor, referred to as Pit-1, appears to bind to all the cell-specific elements in each gene and to be required for the activation of both the prolactin and growth hormone genes. The data suggest that, in the course of development, a single tissue-specific factor activates sets of genes that ultimately exhibit restricted cell-specific expression and define cellular phenotype.
TL;DR: A steroid responsive unit can be composed of several modules that, if positioned correctly, act synergistically, according to the degree of synergism of the GRE.
Abstract: Progesterone (PRE) or glucocorticoid receptor (GRE) DNA binding sites are often found clustered with binding sites for other transcription factors. Individual protein binding sites were tested without the influence of adjacent factors by analyzing isolated combinations of several transcription factor binding sites with PREs or GREs. All show strong synergistic effects on steroid induction. The degree of synergism is inversely related to the strength of the GRE. Thus, a steroid responsive unit can be composed of several modules that, if positioned correctly, act synergistically.
TL;DR: Reconstituted protein-protein and protein-DNA interactions in vitro using Fos and Jun synthesized in reticulocyte lysates demonstrate a cooperative interaction between the protein products of two proto-oncogenes with a DNA element involved in transcriptional regulation.
Abstract: The protein products of the fos (Fos) and jun (Jun) proto-oncogenes have been shown to associate with a DNA element known as the transcription factor activator protein-1 (AP-1) binding site. Jun (previously known as the Fos-binding protein p39) and Fos form a protein complex in the nucleus. To investigate the nature of the association of Fos and Jun with the AP-1 site, and to determine the role of protein complex formation in DNA-binding, we have reconstituted the protein-protein and protein-DNA interactions in vitro using Fos and Jun synthesized in reticulocyte lysates. The Fos-Jun complex formed extremely rapidly in vitro and possessed similar, though not identical, chromatographic and sedimentation properties to the complex isolated from cell extracts. Jun exhibited a low level of AP-1 binding activity; however, this was evident only at high concentrations of DNA. Fos did not bind to the AP-1 site on its own; however, it acted cooperatively with Jun to give enhanced DNA-binding activity. The increased affinity of the Fos-Jun complex for DNA resulted from a stabilization of the protein-DNA complex. These data demonstrate a cooperative interaction between the protein products of two proto-oncogenes with a DNA element involved in transcriptional regulation.
TL;DR: It is shown by gene transfer studies that the same glucocorticoid receptor that activates gene expression can negatively regulate expression of the human glycoprotein hormone alpha-subunit gene.
Abstract: Although steroid hormone receptors are known to activate gene expression by binding to specific hormone-dependent enhancers, the mechanisms by which steroids inhibit the transcription of specific genes are unknown. It is shown here by gene transfer studies that the same glucocorticoid receptor that activates gene expression can negatively regulate expression of the human glycoprotein hormone alpha-subunit gene. Glucocorticoid inhibition was conferred by a 52-nucleotide region that also contains elements crucial both for adenosine 3',5'-monophosphate (cAMP) responsiveness and for placental-specific expression of this gene and was observed only under conditions in which these elements were functioning as enhancers. Purified glucocorticoid receptor was found to bind to DNA that overlap the cAMP responsive elements sites in this region. It is hypothesized that steroid receptors negatively regulate gene expression by interfering with the activity or binding of other important transcription factors.
TL;DR: A protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken beta-globin locus is identified, leading to a loss of enhancing ability byutation of the sites.
Abstract: We have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken beta-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.
TL;DR: It is shown that one of the fos-associated proteins, p39, is immunologically and structurally related to nuclear factor AP-1, and the sequence TGACTCA, which is the consensus minimal binding site of AP- 1, is also recognized by gel-purified p39.
TL;DR: This work has defined the 13 bp palindrome GGTCACAGTGACC as a minimal functional estrogen responsive element (ERE), which binds estrogen receptor preferentially in vitro and point mutations within the ERE decrease its affinity for the estrogen receptor and result in a complete loss of estrogen inducibility.
Abstract: Sequences located upstream of the transcription initiation site of the Xenopus vitellogenin A2 (vit A2) gene contain a hormone dependent enhancer that confers estrogen control to the heterologous thymidine kinase (tk) promoter. As a minimal functional estrogen responsive element (ERE), we have defined the 13 bp palindrome GGTCACAGTGACC. This ERE binds estrogen receptor preferentially in vitro. Although the ERE shares some structural features with the glucocorticoid responsive element (GRE) it is distinct from this element since it neither binds glucocorticoid receptor in vitro nor does it confer glucocorticoid inducibility to a fusion gene. Point mutations within the ERE decrease its affinity for the estrogen receptor and result in a complete loss of estrogen inducibility.
TL;DR: It is demonstrated that the fos protein directly modulates jun function by means of a heterodimer of fos and jun proteins, and a distinct domain, localized in the C-terminal region of thefos protein, is responsible for transcriptional regulation.
Abstract: Gene expression is modulated by the specific interactions of nuclear proteins with unique regulatory sequences in the genome. Proteins involved in transcriptional regulation seem to be either transcription factors or transcription modulators and their interactions are crucial in determining whether the expression of a specific gene is activated or repressed. Recently1, the product of the proto-oncogene jun has been identified as the transcription factor AP-1, whereas nuclear oncoproteins fos and myc have been implicated in transcriptional transregulation of several promoters2–6. Furthermore, the products of the fos and jun proto-oncogenes are associated in some transcription complexes3,5,7. Although the nature of the association is unclear, the two proteins co-immunoprecipitate with fos antibodies in nuclear extracts8–10. Here, we report studies that demonstrate that the fos protein directly modulates jun function by means of a heterodimer of fos and jun proteins. The fos 'leucine zipper'11 domain is necessary for the DNA binding of the heterodimer; a distinct domain, localized in the C-terminal region of the fos protein, is responsible for transcriptional regulation.
TL;DR: Using jun-B as a probe, a cDNA is isolated that is the murine version of the protooncogene c-jun, which encodes the mammalian transcription factor AP-1 and is likely to play a role in regulating the genetic program induced by growth factors.
Abstract: We have previously reported that one of the genes that is rapidly induced in mouse 3T3 cells by serum growth factors (jun-B) encodes a protein related to the onco-protein v-jun. By using jun-B as a probe, we have isolated a cDNA encoding a second member of the jun family (jun-A) that is the murine version of the protooncogene c-jun, which encodes the mammalian transcription factor AP-1. jun-B and jun-A (c-jun) have two highly conserved regions and two regions with little sequence similarity. Like jun-B, jun-A (c-jun) is rapidly activated by serum, platelet-derived growth factor, or fibroblast growth factor and is superinduced by serum in the presence of an inhibitor of protein synthesis. Both jun proteins are likely to play a role in regulating the genetic program induced by growth factors.