Growth Factors Regulate Transin Gene Expression by c-
            <i>fos</i>
            -Dependent and c-
            <i>fos</i>
            -Independent Pathways

Kerr, Lawrence D.; Holt, Jeffrey T.; Matrisian, Lynn M.

doi:10.1126/science.2462278

Cited by 279 publications

(153 citation statements)

References 25 publications

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“…The oligonucleotides employed in the antisense strategies are usually singlestranded DNA, 15 to 30 nucleotides in length. Anti-sense oligodeoxynucleotides have been used to suppress the expression of c-fos gene in cell culture systems [28][29][30][31][32][33][34] and in an animal model [35]. The antisense oligodeoxynucleotides are designed to block selected events such as transcription, splicing, or translation of the target mRNA.…”

Section: Nih Public Accessmentioning

confidence: 99%

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Liu

Salminen

et al. 1994

Annals of Neurology

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Activation of c-fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia. Fos and Jun form a heterodimer as activator protein 1 (AP-1), which transregulates the expression of several genes. To study the postischemic events related to c-fos expression, we suppressed the expression of c-fos by intraventricular infusion of an antisense Oligodeoxynucleotide (anti-rncfosr 115 ) of c-fos mRNA. The effectiveness of antirncfosr 115 was confirmed first by its capability to block in vitro c-fos mRNA translation. In vivo, after intraventricular infusion of 32 P-labeled anti-rncfosr 115 , the oligodeoxynucleotide was internalized within 6 hours and detectable also in the nucleic acids fraction up to 41 hours. Treatment of the recovered nucleic acids with RNase H separated the labeled Oligodeoxynucleotide from the nucleic acid fraction, indicating an association of the antisense Oligodeoxynucleotide and cellular RNA after uptake. When focal cerebral ischemia was induced 16 hours after the infusion of antirncfosr 115 , the postischemic increase in Fos expression and AP-1 binding activity were suppressed. Specificity of the effect of anti-rncfosr 115 was suggested by its failure to suppress the DNA binding activity of nuclear cyclic AMP response elements. These results support the hypothesis that increased AP-1 binding activity following focal cerebral ischemia is dependent on Fos expression and can be inhibited in vivo by antisense c-fos oligodeoxynucleotides.The molecular events of brain adaptation to injury that may underlie functional recovery after stroke remain largely undefined. Recent observations of altered gene expression in ischemic brain using animal stroke models have opened new avenues for exploration of the biochemical cascades after stroke [1][2][3][4][5][6][7][8][9][10][11]. These postischemic events include an increase in extracellular excitatory amino acid neurotransmitters such as glutamate. Glutamate receptor-mediated activation of phospholipases and protein kinases results in the alteration of nuclear regulatory processes, including the expression of immediate early genes such as c-fos, junB, and c-jun [5,12]. The Fos, Jun, and JunB proteins have been shown to form activator protein 1 (AP-1) through a conserved dimerization domain, i.e., the leucine zipper [13]. Transcription regulator AP-1 protein binds a specific DNA motif and is believed to transactivate the expression of a number of late effector genes [14][15][16][17][18][19]. In the ischemic brain, we have previously demonstrated an increase in AP-1 binding activity [9]. A number of genes that bear neurotrophic properties may be regulated by transcription regulator AP-1. These genes, such as heat shock protein [1,4,[19][20][21][22], amyloid [23], neurotrophins [7], and protein tyrosine kinase receptor trkB [24], have been shown to be induced following cerebral ischemia. The causal relationship between the Fos/Jun-AP-1 cascade and the subsequent expression of the late e...

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Section: Nih Public Accessmentioning

confidence: 99%

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Liu

Salminen

et al. 1994

Annals of Neurology

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“…Examples of proteins expressed are type 1 collagenase and stromelysin 1, both of which are proteases that are involved in the degradation of the ECM (Kerr et al, 1988;Schonthal et al, 1988). In order to identify more AP-1 regulated genes that are needed for FBR invasion, we have used di erential screening and subtractive suppression hybridization (Diatchenko et al, 1996;Hennigan et al, 1994;Johnston et al, 1999, unpublished).…”

Section: Introductionmentioning

confidence: 99%

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

et al. 2000

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“…Several AP-1 responsive genes have been identi®ed, like those encoding collagenase or stromelysin/transin (Angel et al, 1987;Kerr et al, 1988), but their possible role in jun-induced cell transformation has not been assessed yet. Recently, approaches aimed at the identi®cation of genes speci®cally dysregulated in juntransformed ®broblasts have led to the identi®cation of two new potential jun target genes.…”

Section: Introductionmentioning

confidence: 99%

Structure and transcriptional regulation of BKJ, a novel AP-1 target gene activated during jun- or fos-induced fibroblast transformation

Hartl

Bister

1998

Oncogene

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The BKJ gene was originally identi®ed based on its speci®c transcriptional activation in jun-transformed avian ®broblasts. We now show that BKJ is a direct transcriptional target of the AP-1 transcription factor components Jun and Fos. The complete structural organization of the quail BKJ gene was determined by nucleotide sequence analysis and transcriptional mapping. The gene contains three exons with the coding region con®ned to the third exon. A major mRNA species of 0.8 kb and a minor one of 1.3 kb are produced by variable usage of two transcriptional initiation sites. The BKJ promoter region contains two authentic AP-1 binding sites. By transactivation of reporter gene constructs and direct binding of Jun recombinant protein, the proximal AP-1 element was shown to be essential for BKJ promoter activation. Using polyclonal antiserum directed against recombinant BKJ protein, the activation of BKJ in jun-transformed avian ®broblasts was also demonstrated at the protein level. BKJ is a novel gene related to the avian b-keratin gene family whose members display highly speci®c expression patterns during embryogenesis and epidermal development. Activation of BKJ in ®broblasts by retroviral or deregulated cellular jun or fos alleles may contribute to cell transformation.

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Growth Factors Regulate Transin Gene Expression by c- fos -Dependent and c- fos -Independent Pathways

Cited by 279 publications

References 25 publications

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

Structure and transcriptional regulation of BKJ, a novel AP-1 target gene activated during jun- or fos-induced fibroblast transformation

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