Effects of human papillomavirus type 16 oncoproteins on survivin gene expression.
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. Transduction 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.
Borbély
Ágnes A
ÁA
Department of Medical Microbiology, Medical and Health Science Centre, University of Debrecen, PO Box 17, H-4012 Debrecen, Hungary.
Murvai
Melinda
M
Tumourvirus Research Group of the Hungarian Academy of Sciences, PO Box 17, H-4012 Debrecen, Hungary.
Kónya
József
J
Department of Medical Microbiology, Medical and Health Science Centre, University of Debrecen, PO Box 17, H-4012 Debrecen, Hungary.
Beck
Zoltán
Z
Department of Medical Microbiology, Medical and Health Science Centre, University of Debrecen, PO Box 17, H-4012 Debrecen, Hungary.
Gergely
Lajos
L
Tumourvirus Research Group of the Hungarian Academy of Sciences, PO Box 17, H-4012 Debrecen, Hungary.|Department of Medical Microbiology, Medical and Health Science Centre, University of Debrecen, PO Box 17, H-4012 Debrecen, Hungary.
Li
Fengzhi
F
Department of Pharmacology and Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Elm & Carlton Street, Buffalo, NY 14263, USA.
Veress
György
G
Department of Medical Microbiology, Medical and Health Science Centre, University of Debrecen, PO Box 17, H-4012 Debrecen, Hungary.
D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D027383:Papillomaviridae / Q000737:chemistry*; D050725:Papillomavirus E7 Proteins; D010957:Plasmids / Q000235:genetics; D012097:Repressor Proteins / Q000494:pharmacology*; D000077022:Survivin
C107489:BIRC5 protein, human; C068651:E6 protein, Human papillomavirus type 16; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D000077022:Survivin; C059731:oncogene protein E7, Human papillomavirus type 16