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Felis catus papillomavirus type-2 E6 binds to E6AP, promotes E6AP/p53 binding and enhances p53 proteasomal degradation.
Altamura, Gennaro; Power, Karen; Martano, Manuela; Degli Uberti, Barbara; Galiero, Giorgio; De Luca, Giovanna; Maiolino, Paola; Borzacchiello, Giuseppe.
Afiliación
  • Altamura G; Department of Veterinary medicine and Animal productions - University of Naples Federico II - Via Veterinaria 1, Naples, 80137, Italy.
  • Power K; Department of Veterinary medicine and Animal productions - University of Naples Federico II - Via Veterinaria 1, Naples, 80137, Italy.
  • Martano M; Department of Veterinary medicine and Animal productions - University of Naples Federico II - Via Veterinaria 1, Naples, 80137, Italy.
  • Degli Uberti B; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, Portici, Naples, 80055, Italy.
  • Galiero G; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, Portici, Naples, 80055, Italy.
  • De Luca G; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, Portici, Naples, 80055, Italy.
  • Maiolino P; Department of Veterinary medicine and Animal productions - University of Naples Federico II - Via Veterinaria 1, Naples, 80137, Italy.
  • Borzacchiello G; Department of Veterinary medicine and Animal productions - University of Naples Federico II - Via Veterinaria 1, Naples, 80137, Italy. borzacch@unina.it.
Sci Rep ; 8(1): 17529, 2018 12 03.
Article en En | MEDLINE | ID: mdl-30510267
E6 from high risk human papillomaviruses (HR HPVs) promotes ubiquitination and degradation of p53 tumour suppressor by mediating its binding to ubiquitin ligase E6AP in a ternary complex, contributing to cell transformation in cervical cancer. We have previously shown that Felis catus papillomavirus type -2 (FcaPV-2) E6 is expressed in feline squamous cell carcinoma (SCC) and displays the ability to bind p53 and decrease its protein levels in transfected CRFK cells. However, the mechanism of p53 downregulation has not yet been characterized. Here we show that FcaPV-2 E6 bound to E6AP, which in turn was bound by p53 exclusively in cells expressing the viral oncoprotein (CRFKE6). Furthermore, p53 was highly poly-ubiquitinated and underwent accumulation upon E6AP gene knockdown in CRFKE6. Half-life experiments and proteasome inhibition treatments indicated that down-regulation of p53 protein in CRFKE6 was due to accelerated proteasomal degradation. E6AP/p53 binding was also demonstrated in two feline SCC cell lines expressing FcaPV-2 E6, where p53 protein levels and poly-ubiquitination degree were proportional to E6 mRNA levels. The data obtained in both artificial and spontaneous in vitro models suggest that FcaPV-2 E6 degrades p53 through a molecular mechanism similar to HR HPVs, possibly contributing to the development of feline SCC.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Enfermedades de los Gatos / Proteínas Oncogénicas Virales / Proteína p53 Supresora de Tumor / Infecciones por Papillomavirus / Ubiquitina-Proteína Ligasas / Complejo de la Endopetidasa Proteasomal / Lambdapapillomavirus / Proteolisis Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Enfermedades de los Gatos / Proteínas Oncogénicas Virales / Proteína p53 Supresora de Tumor / Infecciones por Papillomavirus / Ubiquitina-Proteína Ligasas / Complejo de la Endopetidasa Proteasomal / Lambdapapillomavirus / Proteolisis Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido