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Verfasst von:Soto, Ubaldo [VerfasserIn]   i
 Lengert, Maike [VerfasserIn]   i
 Finzer, Patrick [VerfasserIn]   i
 Zur Hausen, Harald [VerfasserIn]   i
 Rösl, Frank [VerfasserIn]   i
Titel:Conversion of HPV 18 positive non-tumorigenic HeLa-fibroblast hybrids to invasive growth involves loss of TNF-α mediated repression of viral transcription and modification of the AP-1 transcription complex
Verf.angabe:Ubaldo Soto, Bhudev Chandra Das, Maike Lengert, Patrick Finzer, Harald zur Hausen and Frank Rösl
Umfang:12 S.
Fussnoten:Gesehen am 30.01.2019
Titel Quelle:Enthalten in: Oncogene
Jahr Quelle:1999
Band/Heft Quelle:18(1999), 21, S. 3187-3198
ISSN Quelle:1476-5594
Abstract:AP-1 represents a transcription factor, which plays a pivotal role in initiating and maintaining the expression of human papillomavirus (HPV) oncoproteins E6 and E7 during HPV-linked carcinogenesis of the uterine cervix. AP-1 stands as a synonym for different proteins such as c-Jun, JunB, JunD, c-Fos, FosB as well as the Fos-related antigens Fra-1 and Fra-2, which can either homo- or heterodimerize to build up a functional transcription complex. AP-1 is mainly considered as a positive regulator, which binds to cognate DNA sequences within the viral upstream regulatory region. By using non-tumorigenic HeLa-fibroblast hybrids (`444'), their tumorigenic segregants (`CGL3') as well as HPV 18 positive HeLa cells as a experimental model system, evidence is provided that AP-1 composition differs considerably between these cell lines. In nuclear extracts obtained from non-tumorigenic cells, Jun-family members (in the order c-Jun>JunD>JunB) were mainly heterodimerized with Fra-1, a protein, known to be involved in the abrogation of AP-1 activity under certain experimental conditions. In contrast, Fra-1 concentration is low in extracts from tumorigenic cells. Conversely, c-Fos, the canonical dimerization partner of Jun proteins is expressed in substantial quantity in HeLa- and `CGL3' cells, but it is completely absent in AP-1 complexes from non-tumorigenic `444' cells. Ectopical expression of c-fos under a heterologous promoter in `444'-cells induces tumorigenicity and a change of the Jun/Fra-1 ratio towards a constellation initially detected in `CGL3'-and HeLa cells. Furthermore, conversion to tumorigenicity is accompanied with a resistance against TNF-α, a cytokine, capable to selectively suppress HPV 18 transcription in formerly non-malignant cells. These data propose a novel role for AP-1 as an essential component of an inter- and intracellular surveillance mechanism negatively controlling HPV transcription in non-tumorigenic cells.
DOI:doi:10.1038/sj.onc.1202765
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Verlag: http://dx.doi.org/10.1038/sj.onc.1202765
 Verlag: https://www.nature.com/articles/1202765
 DOI: https://doi.org/10.1038/sj.onc.1202765
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1586749196
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