The human papillomavirus-16 e7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin

Anna M. Mileo, Claudia Abbruzzese, Carmen Vico, Emanuele Bellacchio, Paola Matarrese, Barbara Ascione, Antonio Federico, Stefano Della Bianca, Stefano Mattarocci, Walter Malorni, Marco G. Paggi

Research output: Contribution to journalArticle

Abstract

The oncoprotein E7 from human papillomavirus-16 (HPV-16 E7) plays a pivotal role in HPV postinfective carcinogenesis, and its physical interaction with host cell targets is essential to its activity. We identified a novel cellular partner for the viral oncoprotein: the actin-binding protein gelsolin (GSN), a key regulator of actin filament assembly and disassembly. In fact, biochemical analyses, generation of a 3D molecular interaction model and the use of specific HPV-16 E7 mutants provided clear cut evidence supporting the crucial role of HPV-16 E7 in affecting GSN integrity and function in human immortalized keratinocytes. Accordingly, functional analyses clearly suggested that stable HPV-16 E7 expression induced an imbalance between polymeric and monomeric actin in favor of the former. These events also lead to changes of cell cycle (increased S phase), to the inhibition of apoptosis and to the increase of cell survival. These results provide support to the hypotheses generated from the 3D molecular interaction model and encourage the design of small molecules hindering HPV-induced host cell reprogramming by specifically targeting HPV-16 E7-expressing cells.

Original languageEnglish
Pages (from-to)2424-2433
Number of pages10
JournalCarcinogenesis
Volume34
Issue number10
DOIs
Publication statusPublished - Oct 2013

ASJC Scopus subject areas

  • Cancer Research

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