scholarly journals cDNA Cloning of a Novel, Developmentally Regulated Immediate Early Gene Activated by Fibroblast Growth Factor and Encoding a Nuclear Protein

1997 ◽  
Vol 272 (41) ◽  
pp. 25591-25595 ◽  
Author(s):  
Gary D. Paterno ◽  
Yu Li ◽  
H. Artee Luchman ◽  
Paula J. Ryan ◽  
Laura L. Gillespie
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cdna Cloning ◽  
Nuclear Protein ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Fibroblast Growth ◽  
Developmentally Regulated

scholarly journals A novel 7-nucleotide motif located in 3' untranslated sequences of the immediate-early gene set mediates platelet-derived growth factor induction of the JE gene.

1992 ◽  
Vol 12 (12) ◽  
pp. 5288-5300 ◽  
Author(s):  
R R Freter ◽  
J C Irminger ◽  
J A Porter ◽  
S D Jones ◽  
C D Stiles
Keyword(s):  
Growth Factor ◽  
Immediate Early Genes ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Platelet Derived Growth Factor ◽  
Immediate Early ◽  
Control Element ◽  
Gene Set ◽  
Cis Acting ◽  
Early Genes

A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set.

scholarly journals Raf and Fibroblast Growth Factor Phosphorylate Elk1 and Activate the Serum Response Element of the Immediate Early Genepip92 by Mitogen-Activated Protein Kinase-Independent as Well as -Dependent Signaling Pathways

1998 ◽  
Vol 18 (4) ◽  
pp. 2272-2281 ◽  
Author(s):  
Kwang-Chul Chung ◽  
Ignatius Gomes ◽  
Danhui Wang ◽  
Lester F. Lau ◽  
Marsha Rich Rosner
Keyword(s):  
Growth Factor ◽  
Fusion Protein ◽  
Signaling Pathways ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Serum Response Element ◽  
Response Element ◽  
Mitogen Activated Protein ◽  
Serum Response

ABSTRACT Previous studies have shown that a mitogen activated protein (MAP) kinase (MEK)-independent signaling pathway is required by activated Raf or fibroblast-derived growth factor (FGF) for the differentiation of rat hippocampal neuronal H19-7 cells. We now demonstrate that both Raf and FGF similarly induce prolonged transcription and translation of the immediate early gene pip92 in the absence of activation of the MAP kinases (MAPKs) ERK1 and ERK2. To determine the mechanism by which this occurs and to identify novel Raf-activated signaling pathways, we investigated the induction of the pip92promoter by both FGF and an estradiol-activated Raf-1–estrogen receptor fusion protein (ΔRaf-1:ER) in H19-7 cells. Deletion analysis of the pip92 promoter indicated that activation by the MAPK-independent pathway occurs primarily within the region containing a serum response element (SRE). Further analysis of the SRE by using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required. Elk1, which binds to the Ets site, was phosphorylated both in vitro and in vivo by the MAPK-independent pathway, and phosphorylation of an Elk1-GAL4 fusion protein by this pathway was sufficient for transactivation. Finally, at least two Elk1 kinases were fractionated by gel filtration, and analysis by an in-gel kinase assay revealed at least three novel Raf-activated Elk1 kinases. These results indicate that both FGF and Raf activate MAPK-independent kinases that can stimulate Elk1 phosphorylation and immediate early gene transcription.

scholarly journals Engineering combinatorial and dynamic decoders using synthetic immediate-early genes

2019 ◽  
Author(s):  
Pavithran T. Ravindran ◽  
Maxwell Z. Wilson ◽  
Siddhartha G. Jena ◽  
Jared E. Toettcher
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Immediate Early Genes ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Specific Target ◽  
Early Genes

AbstractFor tissues to grow and function properly, cells must coordinate actions such as proliferation, differentiation and apoptosis. This coordination is achieved in part by the activation of intracellular signaling pathways that trigger the expression of context-specific target genes. While the function of these natural circuits has been actively studied, synthetic biology provides additional powerful tools for deconstructing, repurposing, and designing novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (synIEGs), target genes of the Erk signaling pathway that implement complex, user-defined regulation and can be monitored through the use of live-cell biosensors to track transcription and translation. We demonstrate the power and flexibility of this approach by confirming Erk duration-sensing by the FOS immediate-early gene, elucidating how the BTG2 gene is regulated by transcriptional activation and translational repression after growth-factor stimulation, and by designing a synthetic immediate-early gene that responds with AND-gate logic to the combined presence of growth factor and DNA damage stimuli. Our work paves the way to defining the molecular circuits that link signaling pathways to specific target genes, highlighting an important role for post-transcriptional regulation in signal decoding that may be masked by analyses of RNA abundance alone.

A novel 7-nucleotide motif located in 3' untranslated sequences of the immediate-early gene set mediates platelet-derived growth factor induction of the JE gene

1992 ◽  
Vol 12 (12) ◽  
pp. 5288-5300
Author(s):  
R R Freter ◽  
J C Irminger ◽  
J A Porter ◽  
S D Jones ◽  
C D Stiles
Keyword(s):  
Growth Factor ◽  
Immediate Early Genes ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Platelet Derived Growth Factor ◽  
Immediate Early ◽  
Control Element ◽  
Gene Set ◽  
Cis Acting ◽  
Early Genes

A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set.

scholarly journals Methylation of high molecular weight fibroblast growth factor-2 determines post-translational increases in molecular weight and affects its intracellular distribution.

1996 ◽  
Vol 7 (8) ◽  
pp. 1249-1258 ◽  
Author(s):  
G Pintucci ◽  
N Quarto ◽  
D B Rifkin
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
High Molecular Weight ◽  
Nuclear Protein ◽  
Intracellular Distribution ◽  
Nuclear Accumulation ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Post Translational Modification

The high molecular weight (HMW) forms (24, 22.5, and 22 kDa) of basic fibroblast growth factor-2 (FGF-2) contain an N-terminal extension responsible for their predominantly nuclear localization. These forms of FGF-2 are post-translationally modified, resulting in a 1- to 2-kDa increase in apparent molecular mass. Here we show that this post-translational modification is inhibited by methionine starvation and by the methyltransferase inhibitors 5'-deoxy-5'-methylthioadenosine (MTA) and 3-deaza-adenosine. Inhibition of the methylation-dependent modification results in a significant decrease in HMW FGF-2 nuclear accumulation, suggesting that methylation is relevant to the intracellular distribution of these forms of FGF-2. Treatment with MTA does not affect either the synthesis or the intracellular fate of another nuclear protein, the SV40 large T antigen, demonstrating that this drug does not have a generalized effect on nuclear protein accumulation. These results link HMW FGF-2 post-translational modification to its intracellular distribution.

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