title: The human papillomavirus type 16 E5 oncoprotein translocates calpactin I to the perinuclear region.
abstract: The human papillomavirus type 16 (HPV-16) E5 oncoprotein is embedded in membranes of the endoplasmic reticulum and nuclear envelope with its C terminus exposed to the cytoplasm. Among other activities, E5 cooperates with the HPV E6 oncoprotein to induce koilocytosis in human cervical cells and keratinocytes in vitro. The effect of E5 on infected cells may rely on its interactions with various cellular proteins. In this study we identify calpactin I, a heterotetrameric, Ca(2+)- and phospholipid-binding protein complex that regulates membrane fusion, as a new cellular target for E5. Both the annexin A2 and p11 subunits of calpactin I coimmunoprecipitate with E5 in COS cells and in human epithelial cell lines, and an intact E5 C terminus is required for binding. Moreover, E5-expressing cells exhibit a perinuclear redistribution of annexin A2 and p11 and show increased fusion of perinuclear membrane vesicles. The C terminus of E5 is required for both the perinuclear redistribution of calpactin I and increased formation of perinuclear vacuoles. These results support the hypothesis that the E5-induced relocalization of calpactin I to the perinuclear region promotes perinuclear membrane fusion, which may underlie the development of koilocytotic vacuoles.
authors.affiliation: Department of Pathology, Georgetown University Medical School, 3900 Reservoir Road, NW, Washington, DC 20057, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Krawczyk
authors.forename: Frank A
authors.initials: FA
authors.lastname: Suprynowicz
authors.forename: Jess D
authors.initials: JD
authors.lastname: Hebert
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kamonjoh
authors.forename: Richard
authors.initials: R
authors.lastname: Schlegel
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D047468:Immunoprecipitation; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D000086082:Viroporin Proteins
chemical_list: D017306:Annexin A2; D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins