IBA Publikation
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DATUM, UNTERSCHRIFT / DATE, SIGNATURE
BANK AUSTRIA CREDITANSTALT, WIEN (IBAN AT04 1100 0006 2280 0100, BIC BKAUATWW), DEUTSCHE BANK MÜNCHEN (IBAN DE16 7007 0024 0238 8270 00, BIC DEUTDEDBMUC)
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IBA Publikation IBA Publikation
Virology 379
Dieter Morandell,
Ursula Rostek,
Veronique Bouvard,
Beatriz Campo-Fernández,
Marc Fiedler,
Pidder Jansen-Dürr,
Werner Zwerschke
S. 20 - 29 Extern doi:10.1016/j.virol.2008.06.004
Abstract: High-risk human papillomaviruses (HPV) cause cervical cancer. The biological properties of HPV-45, the third most prevalent high-risk HPV-genotype, are unknown. We demonstrate here that the HPV-45 E7-protein transforms immortalized NIH3T3 fibroblasts, while mutations in either the conserved LXCXE sequence (C28G) or the carboxyl-terminus (D87LQQLF91) significantly abolish this activity. To address the mechanisms underlying cell-transformation by HPV-45 E7, we investigated its impact on the cell cycle. We show that HPV-45 E7 associates with the hypophosphorylated form of the retinoblastoma protein (pRb) and induces a significant reduction in the pRb-half-life which can be blocked by epoxomicin. Moreover, HPV-45 E7 induces anchorage-independent cell cycle progression of NIH3T3 cells and extends the lifespan of primary human keratinocytes. HPV-45 E7C28G did not bind pRb and could neither induce pRb-proteolysis nor promote cell cycle progression. HPV-45 E7D87LQQLF91 had intermediate pRb-binding affinity and retained a residual activity to induce the degradation of pRb but lost the capability to promote cell cycle progression in suspension. Another carboxyl-terminal mutant, HPV-45 E7D81AEDL84, showed only a trend to reduced transforming activity, had reduced pRb-binding activity and lost the capability to induce pRbdegradation;however, this mutant could induce anchorage-independent cell cycle progression with the same efficiency as HPV-45 E7 wild type. In summary, these data suggest that HPV-45 E7 is a transforming protein and that abrogation of cell cycle control contributes to its oncogenic potential. Published Online: 2008/09/01 11:11:03 Object Identifier: 0xc1aa5576 0x001b6e87 Rights: .
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epub.oeaw – Institutionelles Repositorium der Österreichischen Akademie der Wissenschaften epub.oeaw – Institutional Repository of the Austrian Academy of Sciences
A-1011 Wien, Dr. Ignaz Seipel-Platz 2
Tel. +43-1-515 81/DW 3420, Fax +43-1-515 81/DW 3400 http://epub.oeaw.ac.at, e-mail: epub@oeaw.ac.at |