Triple Synergism of Human T-Lymphotropic Virus Type 1-Encoded Tax, GATA-Binding Protein, and AP-1 Is Required for Constitutive Expression of the Interleukin-5 Gene in Adult T-Cell Leukemia Cells

Yamagata, Tetsuya; Mitani, Kinuko; Ueno, Hikaru; Kanda, Yoshinobu; Yazaki, Yoshio; Hirai, Hisamaru

doi:10.1128/mcb.17.8.4272

Cited by 44 publications

(36 citation statements)

References 69 publications

(84 reference statements)

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“…Although the peptide epitopes to which the speci®c Jun or Fos antibodies bind are not within the DNA binding domain, the anti c-Jun, anti Jun B, anti c-Fos, and anti Fra-2 antibodies produce blocked shifts rather than supershifts, while the anti Jun D and anti Fra-2 produce a supershift. Similar results have been reported by others (Rosenberger and Bowden, 1996;Joselo and Bowden, 1997;Yamagata et al, 1997). Figure 4b shows that while Jun B was present in the HPV16 series AP-1 complexes, it appeared to be absent from the HPV18 series AP-1/DNA complexes.…”

supporting

confidence: 78%

Expression of dominant negative Jun inhibits elevated AP-1 and NF-κB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes

et al. 1998

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AP-1 transactivation appears to be required for mouse JB6 cell neoplastic transformation induced by the tumor promoter TPA or epidermal growth factor (EGF). Exposure to AP-1 transrepressing retinoids and glucocorticoids and expression of a dominant negative c-jun (TAM67) blocked tumor promoter-induced AP-1 transactivation and neoplastic transformation. The aim of the present study was to extend the inquiry of the role of AP-1 and other transcription factors to human neoplastic progression. Expression of human papillomavirus (HPV) 16 or 18 E6 and E7 immortalizes human keratinocytes and inhibits serum/calcium-stimulated dierentiation. Further transformation by v-fos coexpression renders these keratinocytes tumorigenic in nude mice. We have analysed two series of E6/E7 immortalized human keratinocyte cell lines that show progressing phenotypes ranging from dierentiation sensitive to anchorage-independent to tumorigenic in nude mice. We analysed the activities of AP-1 and NFkB which may`cross-talk'. Both DNA binding and transactivation of AP-1 and NF-kB transcription factors showed elevation in the anchorage-independent (16RH) and tumorigenic (18 v-fos) keratinocyte lines compared to the less progressed but immortalized cell lines. HPV E7 was expressed at a constant level shown by quantitative RT-PCR in both the more and the less progressed lines, indicating that E7 is not the factor limiting this progression. Blocked shift/supershift analysis indicates that Fos family member proteins especially Fra-1 and Fra-2 are related to progression and no changes found in the Jun family member proteins although they are present in the AP-1/DNA binding complex. When a dominant negative mutant cjun driven by a human keratin 14 promoter was cotransfected with AP-1 or NF-kB reporters, both AP-1 and NF-kB activities were suppressed in the more progressed cell lines 16RH and 18 v-fos but not in the less progressed 16RL or 18 cell lines. Overexpression of the same dominant negative c-jun did not inhibit p53 dependent reporter transactivation, indicating the speci®city of inhibition of AP-1 and NF-kB transactivation in the HPV-immortalized cells. Stable transfectants of this mutant c-jun in the two more progressed cell lines 16RH and 18 v-fos showed reduced AP-1 and NF-kB activation and reduced anchorage-independent growth. Together, these results indicate that activation of AP-1, NF-kB or both may contribute to neoplastic progression in HPV immortalized human keratinocytes and that speci®c targeting of the elevated levels seen in benign or malignant tumors might be eective for prevention or treatment of human cancer.

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supporting

confidence: 78%

Expression of dominant negative Jun inhibits elevated AP-1 and NF-κB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes

et al. 1998

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“…These factors may directly interact with ELT-2. Vertebrate GATA-factors interact with a variety of proteins, including AP-1, SP-1, and YY-1 (81)(82)(83)(84)(85)(86)(87). This interaction can result in either the stimulation or repression of transcription.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Metallothionein Gene Transcription

Moilanen¹,

Fukushige²,

Freedman³

1999

Journal of Biological Chemistry

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Metallothioneins are small, cysteine-rich proteins that function in metal detoxification and homeostasis. Metallothionein transcription is controlled by cell-specific factors, as well as developmentally modulated and metal-responsive pathways. By using the nematode Caenorhabditis elegans as a model system, the mechanism that controls cell-specific metallothionein transcription in vivo was investigated. The inducible expression of the C. elegans metallothionein genes, mtl-1 and mtl-2, occurs exclusively in intestinal cells. Sequence comparisons of these genes with other C. elegans intestinal cell-specific genes identified multiple repeats of GATA transcription factor-binding sites (i.e. GATA elements). In vivo deletion and site-directed mutation analyses confirm that one GATA element in mtl-1 and two in mtl-2 are required for transcription. Electrophoretic mobility shift assays show that the C. elegans GATA transcription factor ELT-2 specifically binds to these elements. Ectopic expression of ELT-2 in non-intestinal cells of C. elegans activates mtl-2 transcription in these cells. Likewise, mtl-2 is not expressed in nematodes in which elt-2 has been disrupted. These results indicate that cell-specific transcription of the C. elegans metallothionein genes is regulated by the binding of ELT-2 to GATA elements in these promoters. Furthermore, a model is proposed where ELT-2 constitutively activates metallothionein expression; however, a second metal-responsive factor prevents transcription in the absence of metals. Metallothioneins (MT)1 are a family of structurally related, low molecular weight, cysteine-rich proteins (1). The precise physiological role of MT has not been elucidated. However, evolutionary conservation across many phyla suggests that it serves important roles in cell function. Proposed roles include the following: (a) participation in maintaining the homeostasis of essential trace metals; (b) sequestration of toxic metals, such as cadmium and mercury; (c) acting as a reservoir of essential metals that can be donated to other metalloproteins; and (d) protection against intracellular oxidative damage (2).Exposure of cultured cells or whole organisms to transition metals, ionizing radiation, heat-shock, or oxidative stress induces MT transcription (1, 3-5). Metallothioneins typically occur in multigene families. The mammalian MT family consists of four members designated MT-I to MT-IV (6). It has been commented that all organisms express MT or MT-like proteins. However, not all tissues within an organism will express all MT isoforms. Numerous studies indicate that individual MT family members display specific cellular patterns of expression. Typically, MT-I and MT-II genes are coordinately expressed. It has been shown, however, that MT-2A mRNA levels do not increase in response to cadmium exposure in human proximal tubule cells (7). Expression of the human MT-I B , MT-I E , MT-I F , and MT-I G genes varies in a cell line-specific manner in response to transition metals (8 -12). Mouse MT-I is weakly exp...

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“…During an HTLV-1 infection, a number of cytokines are produced, including IL-1␣, IL-1␤, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-15, TGF-␤, TNF-␣, TNF-␤1, IFN-␥, and GM-CSF (13,22,31,55,85,99,122,161,170,172,176,227,239,258), as well as chemokines such as IL-8, RANTES, and MIP-1␣ (14,169). Constitutive expression of the anti-inflammatory cytokine IL-10 has been shown in ATLL cells and in HTLV-1-infected cell lines (171), thus potentially explaining the state of immune suppression in ATLL.…”

Section: Human T-lymphotropic Virus Typementioning

confidence: 99%

Molecular Pathways in Virus-Induced Cytokine Production

Mogensen

Paludan

2001

Microbiol Mol Biol Rev

373

324

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Virus infections induce a proinflammatory response including expression of cytokines and chemokines. The subsequent leukocyte recruitment and antiviral effector functions contribute to the first line of defense against viruses. The molecular virus-cell interactions initiating these events have been studied intensively, and it appears that viral surface glycoproteins, double-stranded RNA, and intracellular viral proteins all have the capacity to activate signal transduction pathways leading to the expression of cytokines and chemokines. The signaling pathways activated by viral infections include the major proinflammatory pathways, with the transcription factor NF-κB having received special attention. These transcription factors in turn promote the expression of specific inducible host proteins and participate in the expression of some viral genes. Here we review the current knowledge of virus-induced signal transduction by seven human pathogenic viruses and the most widely used experimental models for viral infections. The molecular mechanisms of virus-induced expression of cytokines and chemokines is also analyzed

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Triple Synergism of Human T-Lymphotropic Virus Type 1-Encoded Tax, GATA-Binding Protein, and AP-1 Is Required for Constitutive Expression of the Interleukin-5 Gene in Adult T-Cell Leukemia Cells

Cited by 44 publications

References 69 publications

Expression of dominant negative Jun inhibits elevated AP-1 and NF-κB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes

Expression of dominant negative Jun inhibits elevated AP-1 and NF-κB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes

Regulation of Metallothionein Gene Transcription

Molecular Pathways in Virus-Induced Cytokine Production

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