Effects of human papillomavirus type 16 oncoproteins on survivin gene expression

Ágnes A. Borbély, Melinda Murvai, József Kónya, Zoltán Beck, L. Gergely, Fengzhi Li, G. Veress

Research output: Contribution to journalArticle

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Abstract

Survivin has recently been identified as a novel member of the inhibitor of apoptosis (IAP) gene family. The product of this gene not only suppresses apoptosis but also controls cell division. Survivin is undetectable in most terminally differentiated normal tissues but is expressed in embryonic and fetal organs and is present in most malignant tumours. Human papillomaviruses (HPV) are thought to play an important role in the development of cervical cancer. By interfering in the cell cycle, the viral oncoproteins (E6 and E7) can induce the immortalization of the host cell. The transcriptional effects of the HPV-16 E6 and E7 proteins on the survivin promoter in transiently transfected cell lines using luciferase tests were examined. HPV-16 E6, but not E7, was found to significantly transactivate the survivin promoter. Experiments performed in different cancer cell lines and with different E6 mutants indicated that the effect of E6 on the survivin promoter is largely dependent on p53 status. In accordance with this, the p53 tumour suppressor protein downregulated the expression of survivin. As E6 is able to interact with p53 and induces its ubiquitin-dependent degradation, it appears that the transactivation effect of E6 on survivin is mediated by the p53 degradation pathway. Transcluction of HPV-16 E6 and E7 into human embryonic fibroblast cells showed that the HPV oncoproteins can upregulate endogenous survivin mRNA. Importantly, cell cycle synchronization experiments showed that the effect of HPV-16 E6 on survivin transcription is independent of the cell cycle.

Original languageEnglish
Pages (from-to)287-294
Number of pages8
JournalJournal of General Virology
Volume87
Issue number2
DOIs
Publication statusPublished - Feb 2006

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Human papillomavirus 16
Oncogene Proteins
Cell Cycle
Gene Expression
Papillomavirus E7 Proteins
Apoptosis
Tumor Suppressor Protein p53
Cell Line
Ubiquitin
Luciferases
Uterine Cervical Neoplasms
Cell Division
Transcriptional Activation
Genes
Neoplasms
Up-Regulation
Down-Regulation
Fibroblasts
Messenger RNA

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Effects of human papillomavirus type 16 oncoproteins on survivin gene expression. / Borbély, Ágnes A.; Murvai, Melinda; Kónya, József; Beck, Zoltán; Gergely, L.; Li, Fengzhi; Veress, G.

In: Journal of General Virology, Vol. 87, No. 2, 02.2006, p. 287-294.

Research output: Contribution to journalArticle

Borbély, Ágnes A. ; Murvai, Melinda ; Kónya, József ; Beck, Zoltán ; Gergely, L. ; Li, Fengzhi ; Veress, G. / Effects of human papillomavirus type 16 oncoproteins on survivin gene expression. In: Journal of General Virology. 2006 ; Vol. 87, No. 2. pp. 287-294.
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