The Fos Complex and Fos-Related Antigens Recognize Sequence Elements That Co ntain AP-1 Binding Sites

Franza, B. R.; Rauscher, F. J.; Josephs, S.F.; Curran, Tom

doi:10.1126/science.2964084

Cited by 506 publications

(258 citation statements)

References 29 publications

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“…The potential transcriptional regulation of HIV-1 gene expression by the AP-1 binding site within NRE is further supported by the fact that Curran and his colleagues have identified two additional AP-1 sites in this LTR region (8). However, the novel AP-1 site we found within the TAR region appears to be of even greater interest.…”

Section: Resultssupporting

confidence: 55%

“…Sequences between nucleotides -348 to -343 and -336 to -331 are similar to HeLa cell AP-1 binding sites and have been shown to interact with the FOS-complex and FOS-related antigens (8). In this study we have further examined the HIV-1 LTR, and we have identified three additional AP-1 binding sites one of which was found within the TAR element.…”

Section: Introductionmentioning

confidence: 85%

“…The irans-regulatory element TAR is located between residues -17 to +80. Various cellular proteins have been found to interact with the eis elements, such as AP-1 (8) and USF (9) with NRE; EBP-1 with the enhancer (10); Spi with the sequence motif Spi (11) and TFIID with the TATA box (12). The viral protein Tat interacts with the frans-regulatory element TAR (5,13,14).…”

Section: Introductionmentioning

confidence: 99%

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Ap-1 Recognizes Sequence Elements on Hiv-1 LTR in Human Epithelial Tumor-Cell Lines

Zoumpourlis¹,

Ergazaki²,

Spandidos³

1994

Oncol Rep

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Abstract. Investigation of the nucleotide sequence of the HIV-1 LTR showed the presence of four novel short DNA regions which are homologous to the recognition site for the cellular transcription factor AP-1. Four short oligonucleotide hybrids containing these potential AP-1 sites were constructed and used in gel retardation assays and in competition experiments in order to determine the role of the AP-1 protein in the regulation of HIV-1 expression. The breast MDA MB 468 and cervical HeLa tumor cell lines, which are known to overexpress the AP-1 protein were used in a gel retardation assay as a control to study the affinity of the AP-1 to synthesized oligonucleotide sequences. We have observed specific binding of nuclear factor AP-1 to three of these oligonucleotide hybrids. These results demonstrate the presence of three novel AP-1 binding sites on HIV-1 LTR, one of which was found within the TAR element and in the Tat protein binding region. Moreover, they suggest that AP-1 could be contributing to HIV-1 transcriptional regulation through its interaction with the AP-1 binding sites of HIV-1 LTR.

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Section: Resultssupporting

confidence: 55%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Ap-1 Recognizes Sequence Elements on Hiv-1 LTR in Human Epithelial Tumor-Cell Lines

Zoumpourlis¹,

Ergazaki²,

Spandidos³

1994

Oncol Rep

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“…For example, in the lysis/lysogeny switch of bacteriophage λ, cro and repressor compete for related sites in the rightward operator 28 . In eukaryotes, a number of regulatory proteins have been shown to be members of protein families with related DNA-binding specificities [29][30][31][32][33][34][35][36][37] . In fact, a member of the nuclear hormone receptor family, thyroid hormone receptor, was recently shown to mediate negative effects on transcription from oestrogen-responsive DNA elements, apparently by competing with oestrogen receptor for binding to the elements 38 .…”

Section: Discussionmentioning

confidence: 99%

Activation and repression of transcription by homoeodomain-containing proteins that bind a common site

Jaynes

O’Farrell

1988

Nature

223

148

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The product of the fushi tarazu (ftz) gene is shown to be a site-dependent activator of transcription. In vitro-defined binding sites act as ftz-dependent enhancers in cultured cells. Another homoeodomain-containing protein, the engrailed gene product, competes for homoeodomainbinding sites and counteracts ftz activation.GENETIC analysis in Drosophila melanogaster has identified a group of regulatory genes that participate in embryonic pattern formation 1,2 . Many of these genes encode a 60 amino-acid sequence, the homoeodomain, that is highly conserved through evolution [3][4][5] . This domain contains a putative helix-turn-helix motif 6 such as that found in a number of bacterial regulators 7 , and possesses a sequence-specific DNA-binding activity 8,9 . Numerous regulatory interactions occur among homoeodomain-encoding genes during development. For example, a combination of segmentation and homoeotic gene products, many of which contain homoeodomains 1 , specify the developmental fates of cells in striped patterns 10,11 . Furthermore, homoeodomain-containing proteins (homoeodomain proteins) regulate both each other 12 and downstream (`cytodifferentiation' 13 ) genes. Consequently, it has been attractive to think of homoeodomain proteins as direct regulators of transcription. Due to the complexity of cross-regulatory interactions however, mutations altering or eliminating one homoeodomain protein generally change the expression patterns of many other regulators, confounding efforts to distinguish direct from indirect regulation. Additionally, suspected target genes contain large cis-acting control regions that respond, directly or indirectly, to complex combinations of regulators [14][15][16][17] . As a result, identification of target genes directly regulated by homoeodomain proteins has been problematic.Previous studies have documented instances in which homoeodomain proteins control transcription. The enhancer activity of a DNA fragment from the ftz gene, a homoeodomaincontaining member of the pair-rule class of segmentation genes, suggested that the ftz gene product (ftz) activates its own expression in the embryo 18 . In a different approach a Drosophila tissue culture system was used to show that the Ultrabithorax (Ubx) gene product induces expression of its own promoter, and inhibits the Antennapedia (Antp) (P1) promoter (M. Krasnow and D. S. Hogness, personal communication, see ref. 19 for summary). In these cases however, the complexity of the regulatory circuitry and of the responding control regions leaves open the possibility that the homoeodomain proteins produce these transcriptional effects through intermediaries. To circumvent the complexities of natural target genes, we chose to use binding sites identified in vitro to build homoeodomain-responsive promoters. We find that ftz is a potent activator of transcription from these promoters in cultured cells.During sequential subdivision of the Drosophila embryo to produce segmentally repeating patterns, combinations of regulatory gene prod...

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“…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].…”

mentioning

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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The Fos Complex and Fos-Related Antigens Recognize Sequence Elements That Co ntain AP-1 Binding Sites

Cited by 506 publications

References 29 publications

Ap-1 Recognizes Sequence Elements on Hiv-1 LTR in Human Epithelial Tumor-Cell Lines

Ap-1 Recognizes Sequence Elements on Hiv-1 LTR in Human Epithelial Tumor-Cell Lines

Activation and repression of transcription by homoeodomain-containing proteins that bind a common site

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

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