title: Cutaneous human papillomavirus type 38 E7 regulates actin cytoskeleton structure for increasing cell proliferation through CK2 and the eukaryotic elongation factor 1A.
abstract: We previously reported that the oncoproteins E6 and E7 from cutaneous human papillomavirus type 38 (HPV38) can immortalize primary human keratinocytes in vitro and sensitize transgenic mice to develop skin cancer in vivo. Immunofluorescence staining revealed that human keratinocytes immortalized by HPV38 E6 and E7 display fewer actin stress fibers than do control primary keratinocyte cells, raising the possibility of a role of the viral oncoproteins in the remodeling of the actin cytoskeleton. In this study, we show that HPV38 E7 induces actin stress fiber disruption and that this phenomenon correlates with its ability to downregulate Rho activity. The downregulation of Rho activity by HPV38 E7 is mediated through the activation of the CK2-MEK-extracellular signal-regulated kinase (ERK) pathway. In addition, HPV38 E7 is able to induce actin fiber disruption by binding directly to eukaryotic elongation factor 1A (eEF1A) and abolishing its effects on actin fiber formation. Finally, we found that the downregulation of Rho activity by HPV38 E7 through the CK2-MEK-ERK pathway facilitates cell growth proliferation. Taken together, our data support the conclusion that HPV38 E7 promotes keratinocyte proliferation in part by negatively regulating actin cytoskeleton fiber formation through the CK2-MEK-ERK-Rho pathway and by binding to eEF1A and inhibiting its effects on actin cytoskeleton remodeling.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Jiping
authors.initials: J
authors.lastname: Yue
authors.forename: Ruchi
authors.initials: R
authors.lastname: Shukla
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Zanella-Cleon
authors.forename: Maha
authors.initials: M
authors.lastname: Siouda
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Cros
authors.forename: Vladimir
authors.initials: V
authors.lastname: Krutovskikh
authors.forename: Ishraq
authors.initials: I
authors.lastname: Hussain
authors.forename: Yamei
authors.initials: Y
authors.lastname: Niu
authors.forename: Shiqiong
authors.initials: S
authors.lastname: Hu
authors.forename: Michel
authors.initials: M
authors.lastname: Becchi
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Bakary S
authors.initials: BS
authors.lastname: Sylla
mesh_terms: D000199:Actins / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism*; D015977:Eukaryotic Initiation Factor-1 / Q000037:antagonists & inhibitors*; D006801:Humans; D015603:Keratinocytes / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D011485:Protein Binding
chemical_list: D000199:Actins; D015977:Eukaryotic Initiation Factor-1; D009856:Oncogene Proteins, Viral; D047390:Casein Kinase II