PMID:23729654

Citation	Mileo, AM, Abbruzzese, C, Vico, C, Bellacchio, E, Matarrese, P, Ascione, B, Federico, A, Della Bianca, S, Mattarocci, S, Malorni, W and Paggi, MG (2013) The human papillomavirus-16 E7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin. Carcinogenesis 34:2424-33
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.
Links	PubMed Online version:10.1093/carcin/bgt192
Keywords	Actins/metabolism; Amino Acid Motifs; Amino Acid Sequence; Apoptosis; Caspase 3/metabolism; Cell Line, Tumor; Gelsolin/chemistry; Gelsolin/metabolism; 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
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HPV16:VE7	involved_in	GO:0030838: positive regulation of actin filament polymerization	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:P06396)	Seeded From UniProt	complete
HPV16:VE7	involved_in	GO:0039650: suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P	has_input:(UniProtKB:P42574) has_input:(UniProtKB:P06396)	Seeded From UniProt	complete
HUMAN:CASP3	enables	GO:0097153: cysteine-type endopeptidase activity involved in apoptotic process	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(UniProtKB:P06396)	Seeded From UniProt	complete
HPV16:VE7	colocalizes_with	GO:0042025: host cell nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HPV16:VE7	involved_in	GO:0039650: suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P	has_regulation_target:(UniProtKB:P42574) has_input:(UniProtKB:P06396)	Seeded From UniProt	complete
HPV16:VE7	involved_in	GO:0030838: positive regulation of actin filament polymerization	ECO:0000314: direct assay evidence used in manual assertion		P	has_regulation_target:(UniProtKB:P06396)	Seeded From UniProt	complete
HUMAN:GELS	involved_in	GO:0030041: actin filament polymerization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:GELS	involved_in	GO:1902174: positive regulation of keratinocyte apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:GELS	colocalizes_with	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:CASP3	enables	GO:0097153: cysteine-type endopeptidase activity involved in apoptotic process	ECO:0000314: direct assay evidence used in manual assertion		F	has_direct_input:(UniProtKB:P06396)	Seeded From UniProt	complete

References

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