Kirschberg, Matthias, Heuser, Sandra, Syed, Adnan S., Steger, Gertrud, Majewski, Slawomir, Hufbauer, Martin and Akguel, Baki (2019). HPV8 activates cellular gene expression mainly through Sp1/3 binding sites. Virology, 535. S. 136 - 144. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 0042-6822

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Abstract

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-E7(L23A) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kirschberg, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heuser, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Syed, Adnan S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steger, GertrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Majewski, SlawomirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hufbauer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Akguel, BakiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-143395
DOI: 10.1016/j.virol.2019.06.019
Journal or Publication Title: Virology
Volume: 535
Page Range: S. 136 - 144
Date: 2019
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication: SAN DIEGO
ISSN: 0042-6822
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROTEIN; CARCINOMA; E7; DIFFERENTIATION; INVASION; MATRIX; TUMORS; SP3Multiple languages
VirologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14339

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