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 language | English |
|---|---|
| Pages (from-to) | 2424-2433 |
| Number of pages | 10 |
| Journal | Carcinogenesis |
| Volume | 34 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2013 |
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ASJC Scopus subject areas
- Cancer Research
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The human papillomavirus-16 e7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin. / Mileo, Anna M.; Abbruzzese, Claudia; Vico, Carmen; Bellacchio, Emanuele; Matarrese, Paola; Ascione, Barbara; Federico, Antonio; Bianca, Stefano Della; Mattarocci, Stefano; Malorni, Walter; Paggi, Marco G.
In: Carcinogenesis, Vol. 34, No. 10, 10.2013, p. 2424-2433.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The human papillomavirus-16 e7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin
AU - Mileo, Anna M.
AU - Abbruzzese, Claudia
AU - Vico, Carmen
AU - Bellacchio, Emanuele
AU - Matarrese, Paola
AU - Ascione, Barbara
AU - Federico, Antonio
AU - Bianca, Stefano Della
AU - Mattarocci, Stefano
AU - Malorni, Walter
AU - Paggi, Marco G.
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84885107546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885107546&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgt192
DO - 10.1093/carcin/bgt192
M3 - Article
C2 - 23729654
AN - SCOPUS:84885107546
VL - 34
SP - 2424
EP - 2433
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 10
ER -