The human papillomavirus-16 E7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin

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...

Full description

Saved in:
Bibliographic Details
Published in:Carcinogenesis (New York) 2013-10, Vol.34 (10), p.2424-2433
Main Authors: Mileo, Anna M, Abbruzzese, Claudia, Vico, Carmen, Bellacchio, Emanuele, Matarrese, Paola, Ascione, Barbara, Federico, Antonio, Della Bianca, Stefano, Mattarocci, Stefano, Malorni, Walter, Paggi, Marco G
Format: Article
Language:English
Subjects:
Actins - metabolism
Amino Acid Motifs
Amino Acid Sequence
Apoptosis
Caspase 3 - metabolism
Cell Line, Tumor
Gelsolin - chemistry
Gelsolin - metabolism
Human papillomavirus
Humans
Molecular Docking Simulation
Mutation
Papillomavirus E7 Proteins - chemistry
Papillomavirus E7 Proteins - genetics
Papillomavirus E7 Proteins - metabolism
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgt192