关键词： 转录激活因子3   碱基序列   结合部位   DNA   HeLa细胞   启动区(遗传学)   阻遏蛋白质类/遗传学   TATA盒   转录因子/遗传学   转录因子/代谢   转录   遗传   人类  

摘要： Previously, we demonstrated that ATF3 ((a) under bar ctivating (t) under bar ranscription (f) under bar actor-(3) under bar) is a stress-inducible gene, and the protein it encodes is a transcriptional repressor. In this report, we present evidence suggesting that ATF3 represses the transcription of its own gene. Interestingly, efficient repression requires a consensus ATF/ cAMP-responsive element site in the promoter and a previously unidentified ATF3-binding site immediately downstream from the TATA box. Although this new site resembles the known ATF/cAMP-responsive element sequences at the flanking sequence, it differs from them at the center key residues. These observations indicate that ATF3 can tolerate variations in the center of the binding sites if the flanking sequences are favorable. The repression of the ATF3 promoter by its own gene product provides a mechanistic explanation, at least in part, for the transient expression pattern of the ATF3 gene upon stress induction.

关键词： 转录激活因子3   轴突切断术   生物学标记   神经节   脊/生理学   神经节   脊/病理生理学   基因   jun   亮氨酸拉链   运动神经元/生理学   神经元   传入/生理学   原癌基因蛋白质c-jun/生物合成   RNA   信使/遗传学   坐骨神经/损伤   坐骨神经/生理学   脊髓/生理学   脊髓/病理生理学   转录因子/生物合成   转录因子/遗传学   转录   遗传   动物   大鼠  

摘要： Activating transcription factor 3 (ATF3), a member of ATF/CREB family of transcription factors, is induced in a variety of stressed tissue. ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins. The purpose of this study was to examine the expression and regulation of ATF3 after axonal injury in neurons in dorsal root ganglia (DRG) and spinal cord. In naive rats, ATF3 was not expressed in the DRG and spinal cord. Following the cut of peripheral nerve, ATF3 was immediately induced in virtually all DRG neurons and motoneurons that were axotomized, and the time course of induction was dependent on the distance between the injury site and the cell body. Double labeling using immunohistochemistry revealed that the population of DRG neurons expressing ATF3 included those expressing c-jun, and in motoneurons ATF3 and c-jun were concurrently expressed after axotomy. In contrast to c-jun, ATF3 was not induced transsynaptically in spinal dorsal horn neurons. We conclude that ATF3 is specifically induced in sensory and motoneurons in the spinal cord following nerve injury and should be regarded as an unique neuronal marker of nerve injury in the nervous system.

关键词： IFN gamma   IL-4   LRF-1   ATF3   c-Jun   c-Fos  

摘要： To study macrophage genes activated by lipopolysaccharide (LPS) we have constructed a cDNA library using the mouse macrophage cell line, RAW 264.7. By differential screening, a gene, designated LRG-21, was identified that showed nucleic acid sequence homology to rat liver regenerating factor-1 (LRF-1) and human activating transcription factor-3 (ATF3). Both LRG-21 and LRF-1 are transcribed within an hour following stimulation and in the absence of protein synthesis. The predicted protein sequence of LRG-21 consists of 181 amino acids with a molecular weight of 20.7 kDa. All three sequences contain basic and leucine zipper regions characteristic of the c-Fos and c-Jun family of transcription factors, but the remainder of the sequences are unrelated to this family. Recombinant LRG-21 has been shown to bind to a phorbol ester promoter element. Additional experiments have shown that LRG-21 is also induced by interferon-gamma (IFN-gamma) and by interleukin-4 (IL-4) in both RAW264.7 cells and murine peritoneal macrophages. Based on these observations, it is likely that LRG-21 plays an important role in macrophage activation. Copyright (C) 1996 Elsevier Science Ltd

关键词： Chemical structure   Energy   Anions   Basis sets   Chemical calculations  

摘要： Group 17 element fluorides EF(3) (E = Cl, Br, I) are well-known to undergo second-order Jahn-Teller symmetry breaking toward a T-shaped Ct, arrangement mainly due to a(1)'(HOMO)circle times e'(LUMO) mixing at the expected symmetric trigonal planar D-3h state. For heavy elements, the a(1)'HOMO is relativistically stabilized because of large element s-orbital participation. Hence, relativistic effects diminish the second-order Jahn-Teller term. This results in a large relativistic change in the F-eq-E-F-ax bonding angle of alpha(e)(R) - alpha(e)(NR) = 5.5 degrees in the case of AtF3 and causes an anomaly in the bond angle behavior down the group 17 compounds, alpha(ClF3) > alpha(BrF3) > alpha(AtF3) > alpha(IF3). Furthermore, the difference between the symmetric D-3h and the distorted C-2v structure Of AtF3 is only 10 kJ/mol at the coupled cluster level of theory, indicating that the measured F-eq-At-F-ax angle alpha(e) will be very sensitive upon the temperature applied in gas phase diffraction studies. Vibrational frequencies are predicted for all group 17 fluorides EF(3). As a consequence of the second-order Jahn-Teller distortion, the A(1) symmetric bending mode is strongly influenced by relativistic effects and becomes much lower in frequency compared to the B-1 out of plane mode for the heavier elements. With the exception of IF3, the symmetric D-3h structure represents a (metastable) weak local minimum at the MP2 level, rather than a transition state as expected. The D-3h point represents, however, a second-order saddle point at the HF level, and therefore, electron correlation seems to be responsible for changing the nature of the trigonal planar structure. Extended basis sets at the MP2 level as well as coupled cluster calculations were applied in order to obtain more accurate information for the energetics and structure of CIF3. These studies show, however, that the nature of the D-3h point is critically dependent upon the basis set (and the electron correlat

关键词： Gene Expression Regulation   Promoter Regions (Genetics)   Anisomycin   Base Sequence   Binding Sites   Chloramphenicol O-Acetyltransferase   Consensus Sequence   DNA   DNA Primers   Exons   Genomic Library   Hela Cells   Humans   Introns   Leucine Zippers   Molecular Sequence Data   Plasmids   Protein Synthesis Inhibitors   Proto-Oncogene Proteins c-jun   RNA   Messenger   Recombinant Proteins   Research Support   U.S. Gov't   P.H.S.   Restriction Mapping   TATA Box   Transcription Factors   Transcription   Genetic   Transfection  

摘要： ATF3 gene, which encodes a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses, As a step toward understanding the induction mechanisms, we isolated the human ATF3 gene and analyzed its genome organization and 5'-flanking region. We found that the human ATF3 mRNA is derived from four exons distributed over 15 kilobases. Sequence analysis of the 5'-flanking region revealed a consensus TATA box and a number of transcription factor binding sites including the AP-1, ATF/CRE, NF-kappa B, E2F, and Myc/Max binding sites. As another approach to understanding the mechanisms by which the ATF3 gene is induced by stress signals, we studied the regulation of the ATF3 gene in tissue culture cells by anisomycin, an approach that has been used to study the stress responses in tissue culture cells, We showed that anisomycin at a low concentration activates the ATF3 promoter and stabilizes the ATF3 mRNA, Significantly, co-transfection of DNAs expressing ATF2 and c-Jun activates the ATF3 promoter, A possible mechanism implicating the C-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) stress-inducible signaling pathway in the induction of the ATF3 gene is discussed.

摘要： ATF3 gene, which encodes a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses. As a step toward understanding the induction mechanisms, we isolated the human ATF3 gene and analyzed its genome organization and 5′-flanking region. We found that the human ATF3 mRNA is derived from four exons distributed over 15 kilobases. Sequence analysis of the 5′-flanking region revealed a consensus TATA box and a number of transcription factor binding sites including the AP-1, ATF/CRE, NF-κB, E2F, and Myc/Max binding sites. As another approach to understanding the mechanisms by which the ATF3 gene is induced by stress signals, we studied the regulation of the ATF3 gene in tissue culture cells by anisomycin, an approach that has been used to study the stress responses in tissue culture cells. We showed that anisomycin at a low concentration activates the ATF3 promoter and stabilizes the ATF3 mRNA. Significantly, co-transfection of DNAs expressing ATF2 and c-Jun activates the ATF3 promoter. A possible mechanism implicating the C-Jun NH 2 -terminal kinase/stress-activated protein kinase (JNK/SAPK) stress-inducible signaling pathway in the induction of the ATF3 gene is discussed.

摘要： ATF3 is a member of the mammalian activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors. In this report, we demonstrate that, contrary to the implication of its name, ATF3 represses rather than activates transcription from promoters with ATF sites. We also present evidence suggesting that one possible mechanism by which ATF3 represses transcription is to stabilize inhibitory co-factors at the promoter. In addition, we describe a naturally occurring, alternatively spliced, form of ATF3: ATF3 Delta Zip. ATF3 Delta Zip lacks the leucine zipper domain and does not bind to DNA. In contrast to ATF3, ATF3 Delta Zip stimulates transcription, presumably by sequestering inhibitory co-factors away from the promoter. It is possible that ATF3 Delta Zip is a physiologically important regulator and that it, together with ATF3, regulates the expression of specific target genes.

关键词： AIRCRAFT ENGINES, JET AND TURBINE--Design  

摘要： The ATF3 was designed to give the small executive jet a coast- tocoast range by reducing the fuel consumption by 40% from that of existing engines. The basic engine nominally is sized at the 5000- lb thrust level for sea- level operation.