Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion.
Matthew R. Young,Jian Jian Li,Jian Jian Li,Mercedes Rincon,Richard A. Flavell,B. K. Sathyanarayana,Rosemarie Hunziker,Rosemarie Hunziker,Nancy H. Colburn +8 more
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TLDR
It is concluded that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention.Abstract:
Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. Transactivation of AP-1 is required for tumor promoter-induced transformation in mouse epidermal JB6 cells and for progression in mouse and human keratinocytes. Until now, the question of whether AP-1 transactivation is required for carcinogenesis in vivo has remained unanswered, as has the issue of functionally significant target genes. To address these issues we have generated a transgenic mouse in which transactivation mutant c-jun (TAM67), under the control of the human keratin-14 promoter, is expressed specifically in the basal cells of the epidermis where tumor induction is initiated. The keratin-14–TAM67 transgene was expressed in the epidermis, tongue, and cervix, with no apparent abnormalities in any tissue or organ. TAM67 expression blocked 12-O-tetradecanoylphorbol 13-acetate (TPA, phorbol 12-tetradecanoate 13-acetate) induction of the AP-1-regulated luciferase in AP-1 luciferase/TAM67 mice, but did not inhibit induction of candidate AP-1 target genes, collagenase-1 or stromelysin-3. More interestingly, TAM67 expression did not inhibit TPA-induced hyperproliferation. In two-stage skin carcinogenesis experiments, the transgenic animals showed a dramatic inhibition of papilloma induction. We conclude that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention.read more
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AP-1 as a regulator of cell life and death
Eitan Shaulian,Michael Karin +1 more
TL;DR: Interestingly, the growth-promoting activity of c-Jun is mediated by repression of tumour suppressors, as well as upregulation of positive cell cycle regulators, whereas JunB has the converse effect.
Journal ArticleDOI
AP-1: a double-edged sword in tumorigenesis
Robert Eferl,Erwin F. Wagner +1 more
TL;DR: This work focuses on the JUN and FOS proteins and aims to offer a new perspective on the molecular mechanisms that regulate the oncogenic and anti-oncogenic effects of AP-1 in tumour development.
Journal ArticleDOI
AP-1 in cell proliferation and survival.
Eitan Shaulian,Michael Karin +1 more
TL;DR: Amongst the Jun proteins, c-Jun is unique in its ability to positively regulate cell proliferation through the repression of tumor suppressor gene expression and function, and induction of cyclin D1 transcription.
Journal ArticleDOI
EMT Transition States during Tumor Progression and Metastasis.
TL;DR: The role of the transcriptional and epigenetic landscapes, gene regulatory network and their surrounding niche in controlling the transition through the different EMT states in cancer is summarized.
Journal ArticleDOI
Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth
Francesca Zanconato,Mattia Forcato,Giusy Battilana,Luca Azzolin,Erika Quaranta,Beatrice Bodega,Antonio Rosato,Silvio Bicciato,Michelangelo Cordenonsi,Stefano Piccolo +9 more
TL;DR: This work highlights a new layer of signalling integration, feeding on YAP/TAZ function at the chromatin level, which occurs almost exclusively from distal enhancers that contact target promoters through chromatin looping.
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TL;DR: Results strongly suggest that AP-1 is at the receiving end of a complex pathway responsible for transmitting the effects of phorbol ester tumor promoters from the plasma membrane to the transcriptional machinery.
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The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun.
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TL;DR: The interaction between the lymphoid-specific factor NFATp and the ubiquitous transcription factors Fos and Jun provides a novel mechanism for combinatorial regulation of interleukin-2 gene transcription, which integrates the calcium-dependent and the protein-kinase C-dependent pathways of T-cell activation.
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