Continuous c-fos expression precedes programmed cell death in vivo

Smeyne, Richard J.; Vendrell, Montserrat; Hayward, M. D.; Baker, Suzanne J.; Miao, Graham G.; Schilling, Karl; Robertson, Linda M.; Curran, Tom; Morgan, James I.

doi:10.1038/363166a0

Cited by 750 publications

(311 citation statements)

References 22 publications

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“…Thus, NO produced intracellularly could cause fine modulation of AP-1 activity in vivo through unknown intermediate carriers, the functions of which might be mimicked by SNP and DTT in vitro. Since c-fos induction can be prolonged prior to excitotoxic neuronal cell death [22], such NO-mediated modulation of AP-1 activity in neuronal cells might act as a neuroprotective effector.…”

Section: Resultsmentioning

confidence: 99%

Modulation of AP‐1 activity by nitric oxide (NO) in vitro: NO‐mediated modulation of AP‐1

et al. 1994

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To understand the role of nitric oxide (NO) in controlling the specific DNA-binding activities of transcriptional factors, we investigated the in vitro effect of the NO-donor sodium nitroprusside (SNP) on the AP-1 activity of cultured mouse cerebellar granule cells. A gel-mobility assay showed that SNP inhibited AP-1 activity in the presence, but not the absence of dithiothreitol (DTT). This DTT-dependent inhibition of AP-1 activity by SNP corresponded with the activation of the chemical reactivity of SNP with DTT, which can be monitored by the production of nitrite (NO;). In contrast, diamide, a typical sulfhydryl oxidizing agent, inhibited AP-I activity in the absence of DTT and its inhibitory effect was reversed competitively by DTT. Studies using structurally or functionally related analogues of SNP demonstrated that S-nitrosylation of the AP-1 moiety mediated by some NO-carriers but not by free NO, which can be produced by the chemical reaction of SNP with DTT, was responsible for the inhibition of AP-1 activity, suggesting NO-mediated regulation of the AP-1 transcriptional factor.

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Section: Resultsmentioning

confidence: 99%

Modulation of AP‐1 activity by nitric oxide (NO) in vitro: NO‐mediated modulation of AP‐1

et al. 1994

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“…Using fos-lacZ transgenic mice, containing a fos-lacZ fusion gene, it was demonstrated that continuous high expression of fos-lacZ is evident in skin, hair follicles, and bone cells undergoing terminal di erentiation which culminates in apoptotic cell death (Smeyne et al, 1992). Using the same approach, it was also shown that high constitutive expression of fos was evident in sites of naturally occurring cell death (Smeyne et al, 1993). Using Fos and c-jun de®cient mice, it was found that apoptosis can proceed normally during embryonic development of certain tissues and in some adult organs, such as the thymus and ovary, in the absence of Fos and/or Jun (Ro er- Tarlov et al, 1996).…”

Section: Ap-1 (Fos/jun) Transcription Factors As Positive and Negativmentioning

confidence: 99%

MyD genes in negative growth control

Liebermann

Hoffman

1998

Oncogene

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“…Recent studies describe c-jun and c-fos expression as associated with programmed cell death (Smeyne et al, 1993;Manome et al, 1993;Kim and Beck, 1994), multidrug-resistant phenotype (Scanlon et al, 1994), and deregulated expression has been discussed as a prerequisite of their transforming potential (Miller et al, 1984;Bos et al, 1990;Lee et al, 1988;van den Berg et al, 1993 (Hartmann Analytic, Braunschweig, Germany) by random hexamer priming (Feinberg and Vogelstein, 1983 [100 mM Tris-HCl, pH 7.5, 500 mM sodium chloride, 10 mM EDTA, 50% (v/v) glycerol, 2 mM DTT, 2 pl 1% (v/v) Nonidet P 40] (Sigma), and approximately 10 000 c.p.m. of a y-32P-labelled dsDNA probe with a specific activity not less than 3000 Ci mmol-'.…”

mentioning

confidence: 99%

Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy

Kick

Messer²,

Plewig³

et al. 1996

Br J Cancer

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SummaryPhotodynamic therapy (PDT) is currently under investigation in phase II and III clinical studies for the treatment of tumours in superficial localisations. Thus far, the underlying mechanisms of PDT regarding cellular responses and gene regulation are poorly understood. Photochemically generated singlet oxygen (102) is mainly responsible for cytotoxicity induced by PDT. If targeted cells are not disintegrated, photo-oxidative stress leads to transcription and translation of various stress response and cytokine genes. Tumour necrosis factor (TNF) a, interleukin (IL) 1 and IL-6 are strongly induced by photodynamic treatment, supporting inflammatory action and immunological anti-tumour responses. To investigate the first steps of gene activation, this study focused on the proto-oncogenes c-jun and c-fos, both coding for the transcription factor activator protein 1 (AP-1), which was found to mediate IL-6 gene expression. We here determine the effects of photodynamic treatment on transcriptional regulation and DNA binding of transcription factor AP-1 in order to understand the modulation of subsequent regulatory steps. Photodynamic treatment of epithelial HeLa cells was performed by incubation with Photofrin and illumination with 630 nm laser light in vitro. Expression of the c-jun and c-fos genes was determined by way of Northern blot analysis, and DNA-binding activity of the transcription factor AP-1 was evaluated by electrophoretic mobility shift assay (EMSA). Photofrin-mediated photosensitisation of HeLa cells resulted in a rapid and dose-dependent induction of both genes but preferential expression of c-jun. Compared with the transient expression of c-jun and c-fos by phorbol ester stimulation, photodynamic treatment led to a prolonged activation pattern of both immediate early genes. Furthermore, mRNA stability studies revealed an increased half-life of c-jun and c-fos transcripts resulting from photosensitisation. Although mRNA accumulation after PDT was stronger and more prolonged compared with phorbol ester stimulation, with regard to AP-1 DNA-binding activity, phorbol ester was more efficient. Surprisingly, in addition to the activation of AP-1 DNA-binding via PDT, photodynamic treatment can decrease AP-1 DNA-binding of other strong inducers, such as the protein kinase C-mediated pathway of phorbol esters and the antioxidant pyrrolidine dithiocarbamate (PDTC). This study demonstrates a strong induction of c-jun and c-fos expression by PDT, with prolonged kinetics and mRNA stabilisation as compared with activation by phorbol esters. Interestingly, this observation is not coincident with an overinduction of AP-1 DNA-binding, hence suggesting that post-translational modifications are dominant regulatory mechanisms after PDT that tightly control AP-1 activity in the nucleus thus limiting the risk of deregulated oncogene expression.

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Continuous c-fos expression precedes programmed cell death in vivo

Cited by 750 publications

References 22 publications

Modulation of AP‐1 activity by nitric oxide (NO) in vitro: NO‐mediated modulation of AP‐1

Modulation of AP‐1 activity by nitric oxide (NO) in vitro: NO‐mediated modulation of AP‐1

MyD genes in negative growth control

Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy

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