fra-1: a serum-inducible, cellular immediate-early gene that encodes a fos-related antigen

1988 ◽  
Vol 8 (5) ◽  
pp. 2063-2069 ◽  
Author(s):  
D R Cohen ◽  
T Curran
Keyword(s):  
Regulatory Protein ◽  
Transcriptional Response ◽  
Early Gene ◽  
Immediate Early ◽  
Cdna Clones ◽  
Protein Synthesis Inhibitors ◽  
Amino Acid Homology ◽  
Serum Stimulation ◽  
Fos Protein ◽  
Genes Encoding

A set of proteins antigenically related to the c-fos protein (Fos) are induced by serum in fibroblasts. To isolate cDNA clones of genes encoding such proteins, a lambda gt11 expression cDNA library constructed from serum-stimulated rat fibroblasts was screened with antibodies raised against a hydrophilic region (amino acids 127 to 152) of Fos. One of the positive clones identified, termed fra-1 (Fos-related antigen) was characterized. It encoded a protein that shared several regions of extensive amino acid homology with Fos (including the region that showed similarity to both the yeast GCN4 regulatory protein and the protein encoded by the jun oncogene), although its nucleotide sequence was considerably diverged from that of the c-fos gene. Only a subset of the agents and conditions that activated c-fos also induced fra-1. Induction of fra-1 expression following serum stimulation was delayed compared with that of c-fos. However, like c-fos, fra-1 was induced rapidly by serum in the presence of protein synthesis inhibitors. Thus, a family of Fos-related, inducible genes are involved in the cellular immediate-early transcriptional response to extracellular stimuli.

scholarly journals fra-1: a serum-inducible, cellular immediate-early gene that encodes a fos-related antigen.

1988 ◽  
Vol 8 (5) ◽  
pp. 2063-2069 ◽  
Author(s):  
D R Cohen ◽  
T Curran
Keyword(s):  
Regulatory Protein ◽  
Transcriptional Response ◽  
Early Gene ◽  
Immediate Early ◽  
Cdna Clones ◽  
Protein Synthesis Inhibitors ◽  
Amino Acid Homology ◽  
Serum Stimulation ◽  
Fos Protein ◽  
Genes Encoding

A set of proteins antigenically related to the c-fos protein (Fos) are induced by serum in fibroblasts. To isolate cDNA clones of genes encoding such proteins, a lambda gt11 expression cDNA library constructed from serum-stimulated rat fibroblasts was screened with antibodies raised against a hydrophilic region (amino acids 127 to 152) of Fos. One of the positive clones identified, termed fra-1 (Fos-related antigen) was characterized. It encoded a protein that shared several regions of extensive amino acid homology with Fos (including the region that showed similarity to both the yeast GCN4 regulatory protein and the protein encoded by the jun oncogene), although its nucleotide sequence was considerably diverged from that of the c-fos gene. Only a subset of the agents and conditions that activated c-fos also induced fra-1. Induction of fra-1 expression following serum stimulation was delayed compared with that of c-fos. However, like c-fos, fra-1 was induced rapidly by serum in the presence of protein synthesis inhibitors. Thus, a family of Fos-related, inducible genes are involved in the cellular immediate-early transcriptional response to extracellular stimuli.

scholarly journals The Immediate-Early Gene Product Encoded by Open Reading Frame 57 of Herpesvirus Saimiri Modulates Gene Expression at a Posttranscriptional Level

1998 ◽  
Vol 72 (1) ◽  
pp. 857-861 ◽  
Author(s):  
Adrian Whitehouse ◽  
Matthew Cooper ◽  
David M. Meredith
Keyword(s):  
Gene Expression ◽  
Gene Product ◽  
Target Gene ◽  
Immediate Early Gene ◽  
Open Reading Frame ◽  
Early Gene ◽  
Immediate Early ◽  
Herpesvirus Saimiri ◽  
Amino Acid Homology ◽  
Reading Frame

ABSTRACT The herpesvirus saimiri (HVS) immediate-early gene product encoded by open reading frame (ORF) 57 shares limited amino acid homology with HSV-1 ICP27 and Epstein-Barr virus BMLF1, both regulatory proteins. The ORF 57 gene has been proposed to be spliced based on the genome sequence, and here we confirm the intron-exon structure of the gene. We also demonstrate that a cDNA construct of the ORF 57 gene product represses the transactivating capability of the ORF 50a gene product (which is produced from a spliced transcript), but activates that of ORF 50b (an unspliced transcript). Further analyses with cotransfection experiments show that ORF 57 can either activate or repress expression from a range of both early and late HVS promoters, depending on the target gene. These results indicate that repression of gene expression mediated by the ORF 57 gene product is dependent on the presence of an intron within the target gene encoding region. Furthermore, Northern blot analysis demonstrates that the levels of mRNA transcribed from genes not containing an intron are not significantly affected in the presence of the ORF 57 gene product. This suggests that it regulates gene expression through a posttranscriptional mechanism.

scholarly journals Expression of the Immediate Early Gene c-fos in Basal Ganglia: Induction by Dopaminergic Drugs

1991 ◽  
Vol 18 (S3) ◽  
pp. 380-383 ◽  
Author(s):  
H.A. Robertson ◽  
M.L. Paul ◽  
R. Moratalla ◽  
A.M. Graybiel
Keyword(s):  
Dopamine Agonists ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Dopaminergic Drugs ◽  
Protein Levels ◽  
Selective Antagonists ◽  
Fos Protein ◽  
High Doses

ABSTRACT:Expression of the immediate early gene c-fos is increased in mammalian neurons by a number of stimuli and the usefulness of this gene as a marker of neuronal activation has been demonstrated in several systems. Directlyacting dopamine agonists of the D1-type (SKF 38393, CY 208-243) and indirectly-acting dopamine gonists (amphetamine, cocaine) all produce a rapid and transient increase in Fos protein levels in varying patterns in striatum and cerebral cortex. irectly-acting dopamine agonists only produce c-fos activation in denervated (supersensitive) striatum whereas cocaine and amphetamine activate c-fos in striatum in naive animals. Remarkably, D2 selective antagonists such as haloperidol, albeit in high doses, also activate c-fos expression. Activation of c-fos and other immediate early genes may play a part in the development of such long-term dopamine-related effects as dyskinetic movements and addiction.

Expression of cyr61, a growth factor-inducible immediate-early gene

1990 ◽  
Vol 10 (7) ◽  
pp. 3569-3577
Author(s):  
T P O'Brien ◽  
G P Yang ◽  
L Sanders ◽  
L F Lau
Keyword(s):  
Growth Factor ◽  
Signal Sequence ◽  
Mrna Level ◽  
Immediate Early Genes ◽  
Early Gene ◽  
Immediate Early ◽  
Early Genes ◽  
Serum Stimulation ◽  
3T3 Fibroblasts ◽  
Kinase C

A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cell growth. We show here that a member of this set of genes, cyr61 (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr61 mRNA is accumulated from the G0/G1 transition through mid-G1. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the G0/G1 transition and in mid-G1 at the same rate. In logarithmically growing cells, the cyr61 mRNA level is constant throughout the cell cycle. Cyr61 contains an N-terminal secretory signal sequence; however, it is not detected in the culture medium by immunoprecipitation. Cyr61 is synthesized maximally at 1 to 2 h after serum stimulation and has a short half-life within the cell.

scholarly journals Global Transcriptional Response of Bacillus subtilis to Treatment with Subinhibitory Concentrations of Antibiotics That Inhibit Protein Synthesis

2005 ◽  
Vol 49 (5) ◽  
pp. 1915-1926 ◽  
Author(s):  
Janine T. Lin ◽  
Mariah Bindel Connelly ◽  
Chris Amolo ◽  
Suzie Otani ◽  
Debbie S. Yaver
Keyword(s):  
Protein Synthesis ◽  
Bacillus Subtilis ◽  
Time Course ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Global Gene Expression ◽  
Protein Synthesis Inhibitors ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Subinhibitory Concentrations

ABSTRACT Global gene expression patterns of Bacillus subtilis in response to subinhibitory concentrations of protein synthesis inhibitors (chloramphenicol, erythromycin, and gentamicin) were studied by DNA microarray analysis. B. subtilis cultures were treated with subinhibitory concentrations of protein synthesis inhibitors for 5, 15, 30, and 60 min, and transcriptional patterns were measured throughout the time course. Three major classes of genes were affected by the protein synthesis inhibitors: genes encoding transport/binding proteins, genes involved in protein synthesis, and genes involved in the metabolism of carbohydrates and related molecules. Similar expression patterns for a few classes of genes were observed due to treatment with chloramphenicol (0.4× MIC) or erythromycin (0.5× MIC), whereas expression patterns of gentamicin-treated cells were distinct. Expression of genes involved in metabolism of amino acids was altered by treatment with chloramphenicol and erythromycin but not by treatment with gentamicin. Heat shock genes were induced by gentamicin but repressed by chloramphenicol. Other genes induced by the protein synthesis inhibitors included the yheIH operon encoding ABC transporter-like proteins, with similarity to multidrug efflux proteins, and the ysbAB operon encoding homologs of LrgAB that function to inhibit cell wall cleavage (murein hydrolase activity) and convey penicillin tolerance in Staphylococcus aureus.

Comparative transcriptome analysis of leaves from two grapevine species reveals an early gene expression profile associated with Elsinoe ampelina resistance

2020 ◽  
Author(s):  
Min Gao ◽  
Ran Wan ◽  
Yanxun Zhu ◽  
Chen Jiao ◽  
Chenxia Cheng ◽  
...  
Keyword(s):  
Post Infection ◽  
Defense Mechanisms ◽  
Transcriptional Response ◽  
Enrichment Analysis ◽  
Early Gene ◽  
Pathway Enrichment Analysis ◽  
Genes Encoding ◽  
Elsinoe Ampelina ◽  
Metabolite Synthesis ◽  
Encoding Protein

Abstract Background: Anthracnose ( Elsinoe ampelina ) causes extensive damage to grapevine ( Vitis vinifera ) production worldwide, but the defense mechanisms exhibited by grape are not well understood. Results: In present study, the transcriptome differences of two grape species that exhibit either strong resistance (HR) or sensitivity (HS) to E . ampelina were determined at different time points up to 72 hours post infection (hpi) using RNA-seq profiling. Approximately 172 million high quality reads were obtained from a total of 40 samples. As a result, 3414 differentially expressed genes (DEGs) were identified, with 2,246 in the HR grape V . q uinquangularis Shang-24 accession and 2,019 in the HS grape V . vinifera Red Globe. More up-regulated than down-regulated genes were identified both in the HR and HS samples at each time point except 48 hours post infection. Conclusions: Gene ontology (GO) function and pathway enrichment analysis suggested that the grape transcriptional response to E . ampelina infection involves genes encoding protein kinases, transcription factors, metabolite synthesis, and phytohormone signaling. Although most of the GO functional categories and enriched pathways in response to E . ampelina infection were the same in the two species, the response was apparent much earlier in the HR grape (6 hours post infection and 24 hours post infection) than in the HS grape (48 hours post infection and 72 hours post infection), which may be associated with the contrasting resistance phenotypes. This study provides new insights into the grape defense system involved in responses to E . ampelina infection, and has identified several candidate genes that may be exploited in future biotechnological approaches to increase disease resistance in grapevine.

scholarly journals Identification and Analysis of the K5 Gene of Kaposi's Sarcoma-Associated Herpesvirus

2000 ◽  
Vol 74 (6) ◽  
pp. 2867-2875 ◽  
Author(s):  
Muzammel Haque ◽  
Jiguo Chen ◽  
Keiji Ueda ◽  
Yasuko Mori ◽  
Kazusi Nakano ◽  
...  
Keyword(s):  
Gene Product ◽  
Kaposi's Sarcoma ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Northern Blotting ◽  
Early Gene ◽  
Immediate Early ◽  
Protein Synthesis Inhibitors ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), belongs to the gammaherpesvirus subfamily and encodes ∼80 open reading frames (ORFs). Among them are a few candidates for immediate-early genes (e.g., K5). We developed a monoclonal antibody (MAb), 328C7, against the K5 antigen. This MAb reacted with the K5 gene product by immunoscreening of a cDNA library from BCBL-1 cells, and this result was confirmed by transfection of the K5 ORF into Cos-7 cells. After induction of lytic infection by treatment with 12-O-tetradecanoylphorbol-13-acetate, MAb 328C7 reacted with an antigen in the cytoplasm of BCBL-1 and BC-3 cells as early as after 4 h of induction. Immunoelectron microscopy showed that the K5 antigen was situated mainly in the endoplasmic reticulum but was not present on the virion or in the nucleus. Northern blotting with a K5-specific probe revealed a single transcript of 1.2 kb, while Western blotting showed the antigen to be a 36-kDa polypeptide. The 5′ and 3′ ends were then determined by rapid amplification of cDNA, followed by sequencing of RACE products, and a splice was revealed upstream of the K5 ORF. K5 expression was unaffected by the respective DNA and protein synthesis inhibitors phosphonoformic acid and cycloheximide plus actinomycin D, confirming its immediate-early nature. Transient-transfection assays showed that the K5 promoter was transactivated by ORF 50 (KSHV Rta), a homolog of Epstein-Barr virus Rta, but the K5 gene product exhibited no transregulation of its own promoter or those of DNA polymerase and the human immunodeficiency virus type 1 long terminal repeat. This is the first such analysis of an immediate-early gene product; determination of its specific biological function requires further investigation.

scholarly journals Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1.

1995 ◽  
Vol 15 (9) ◽  
pp. 4930-4938 ◽  
Author(s):  
R Zinck ◽  
M A Cahill ◽  
M Kracht ◽  
C Sachsenmaier ◽  
R A Hipskind ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Immediate Early ◽  
Protein Synthesis Inhibitors ◽  
Mitogen Activated Protein

Inhibitors of protein synthesis, such as anisomycin and cycloheximide, lead to superinduction of immediate-early genes. We demonstrate that these two drugs activate intracellular signaling pathways involving both the mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) cascades. The activation of either pathway correlates with phosphorylation of the c-fos regulatory transcription factor Elk-1. In HeLa cells, anisomycin stabilizes c-fos mRNA when protein synthesis is inhibited to only 50%. Under these conditions, anisomycin, in contrast to cycloheximide, rapidly induces kinase activation and efficient Elk-1 phosphorylation. However, full inhibition of translation by either drug leads to prolonged activation of SAPK activity, while MAPK induction is transient. This correlates with prolonged Elk-1 phosphorylation and c-fos transcription. Elk-1 induction and c-fos activation are also observed in KB cells, in which anisomycin strongly induces SAPKs but not MAPKs. Purified p54 SAPK alpha efficiently phosphorylates the Elk-1 C-terminal domain in vitro and comigrates with anisomycin-activated kinases in in-gel kinase assays. Thus, Elk-1 provides a potential convergence point for the MAPK and SAPK signaling pathways. The activation of signal cascades and control of transcription factor function therefore represent prominent processes in immediate-early gene superinduction.

c-fos mRNA and FOS protein expression is induced by Ca2+ influx in GH3B6 pituitary cells

1996 ◽  
Vol 16 (3) ◽  
pp. 229-238 ◽  
Author(s):  
S L Li ◽  
N Cougnon ◽  
L Bresson-Bépoldin ◽  
S J Zhao ◽  
W Schlegel
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Early Gene ◽  
Immediate Early ◽  
Pituitary Cells ◽  
Protein Species ◽  
Cam Kinase ◽  
Mrna Induction ◽  
Kinase C ◽  
Fos Protein

ABSTRACT The expression of the immediate early gene c-fos was studied at the mRNA and the protein level in cells of the pituitary tumour cell line GH3B6. The induction of c-fos mRNA as detected by Northern blot analysis was stimulated by TRH and by depolarization with KCl, both leading to a rise in cytosolic free [Ca2+] ([Ca2+]i), and also by epidermal growth factor (EGF). To assess the role of the changes in [Ca2+]i in the induction of c-fos, Ca2+ was chelated in the extracellular medium with EGTA to prohibit Ca2+ influx during stimulation, or intracellular Ca2+ stores were emptied by prolonged exposure to EGTA, a treatment which abolished all [Ca2+]i changes. In the latter case, the effect of TRH on c-fos mRNA expression was almost completely abolished, whereas EGF still caused substantial c-fos induction. Full induction of c-fos mRNA by TRH required a prolonged phase of stimulated Ca2+ influx. c-fos mRNA induction by TRH and KCl was markedly inhibited by two blockers of Ca2+/calmodulin-dependent protein kinase (CaM kinase), KN-62 and calmidazolium. In contrast, KCl induction of c-fos and the effects of KN-62 on TRH induction of c-fos were not observed in a closely related pituitary line GH4C1 in which TRH exerts its effects on immediate early genes predominantly via the protein kinase C pathway. In GH3B6 cells stimulated with TRH or KCl, enhanced FOS protein levels were detected by immunofluorescence and localized in the nucleus with confocal microscopy. Analysis by immunoblotting showed that TRH induced two protein species with apparent molecular masses of 52 and 57 kDa. In GH3B6 cells stimulated with KCl or TRH, the 52 kDa species was mainly found whereas, in the GH4C1 cells, TRH predominantly stimulated the 57 kDa species. These data show that distinct signalling pathways (CaM kinase and protein kinase C) involve Ca2+ influx to induce the transcription of the early gene c-fos, and that the resulting FOS protein species may depend on the pathways involved.

scholarly journals Expression of cyr61, a growth factor-inducible immediate-early gene.

1990 ◽  
Vol 10 (7) ◽  
pp. 3569-3577 ◽  
Author(s):  
T P O'Brien ◽  
G P Yang ◽  
L Sanders ◽  
L F Lau
Keyword(s):  
Growth Factor ◽  
Signal Sequence ◽  
Mrna Level ◽  
Immediate Early Genes ◽  
Early Gene ◽  
Immediate Early ◽  
Early Genes ◽  
Serum Stimulation ◽  
3T3 Fibroblasts ◽  
Kinase C

A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cell growth. We show here that a member of this set of genes, cyr61 (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr61 mRNA is accumulated from the G0/G1 transition through mid-G1. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the G0/G1 transition and in mid-G1 at the same rate. In logarithmically growing cells, the cyr61 mRNA level is constant throughout the cell cycle. Cyr61 contains an N-terminal secretory signal sequence; however, it is not detected in the culture medium by immunoprecipitation. Cyr61 is synthesized maximally at 1 to 2 h after serum stimulation and has a short half-life within the cell.

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