| Online-Ressource |
Verfasst von: | Soto, Ubaldo [VerfasserIn]  |
| Lengert, Maike [VerfasserIn]  |
| Finzer, Patrick [VerfasserIn]  |
| Zur Hausen, Harald [VerfasserIn]  |
| Rösl, Frank [VerfasserIn]  |
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 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
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 |
Verknüpfungen: | → Zeitschrift |
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 / Soto, Ubaldo [VerfasserIn] (Online-Ressource)