title: Expression of HPV16 E5 produces enlarged nuclei and polyploidy through endoreplication.
abstract: Anogenital cancers and head and neck cancers are causally associated with infection by high-risk human papillomavirus (HPV). The mechanism by which high-risk HPVs contribute to oncogenesis is poorly understood. HPV16 encodes three genes (HPV16 E5, E6, and E7) that can transform cells when expressed independently. HPV16 E6 and E7 have well-described roles causing genomic instability and unregulated cell cycle progression. The role of HPV16 E5 in cell transformation remains to be elucidated. Expression of HPV16 E5 results in enlarged, polyploid nuclei that are dependent on the level and duration of HPV16 E5 expression. Live cell imaging data indicate that these changes do not arise from cell-cell fusion or failed cytokinesis. The increase in nuclear size is a continual process that requires DNA synthesis. We conclude that HPV16 E5 produces polyploid cells by endoreplication. These findings provide insight into how HPV16 E5 can contribute to cell transformation.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Lulin
authors.initials: L
authors.lastname: Hu
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Potapova
authors.forename: Shibo
authors.initials: S
authors.lastname: Li
authors.forename: Susannah
authors.initials: S
authors.lastname: Rankin
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Gorbsky
authors.forename: Peter C
authors.initials: PC
authors.lastname: Angeletti
authors.forename: Brian P
authors.initials: BP
authors.lastname: Ceresa
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000821:virology; D053144:Cell Nucleus Shape; D002472:Cell Transformation, Viral; D004261:DNA Replication; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051379:Mice; D018715:Microscopy, Video / Q000379:methods; D041681:NIH 3T3 Cells; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011123:Polyploidy; D000086082:Viroporin Proteins
chemical_list: D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins