HPV8 activates cellular gene expression mainly through Sp1/3 binding sites
| Autor: | Baki Akgül, Martin Hufbauer, Slawomir Majewski, Adnan S. Syed, Matthias Kirschberg, Sandra Heuser, Gertrud Steger |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
Carcinogenesis Sp1 Transcription Factor Papillomavirus E7 Proteins Mutant Cell Line 03 medical and health sciences Virology Gene expression medicine Humans Binding site Papillomaviridae 030304 developmental biology 0303 health sciences Binding Sites biology Gene Expression Profiling 030302 biochemistry & molecular biology Promoter medicine.disease Microarray Analysis Cell biology Fibronectins Fibronectin medicine.anatomical_structure Sp3 Transcription Factor Gene Expression Regulation Host-Pathogen Interactions biology.protein Skin cancer Sequence motif Keratinocyte |
| Zdroj: | Virology. 535 |
| ISSN: | 1096-0341 |
| Popis: | The human papillomavirus type 8 (HPV8) is associated with skin cancer development. The goal of this study was to investigate the effects of HPV8 oncoproteins on cellular gene expression and the identification of key regulators. We performed affymetrix microarray analyses to identify differentially expressed genes and common sequence motifs and identified Sp1/3 binding sites as being crucial. In transient transfection assays, we confirmed that HPV8-E7 stimulates the activity of Sp1/3 promoters. Interestingly, the HPV8-E7L23A mutant, which cannot trigger keratinocyte invasion was unable to activate fibronectin gene expression. In skin models or HPV8 positive skin cancers we found a peculiar deposition of fibronectin in the dermal compartment, and a correlation of Sp3 and fibronectin in the nucleus of HPV8-positive keratinocytes. Taken together, we identified that HPV8-E7 exerts control over cellular gene expression through Sp1/3 binding motifs, which may contribute to HPV8-mediated keratinocyte transformation and subsequent fibronectin-dependent invasion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect