title: Skin human papillomavirus type 38 alters p53 functions by accumulation of deltaNp73.
abstract: The E6 and E7 of the cutaneous human papillomavirus (HPV) type 38 immortalize primary human keratinocytes, an event normally associated with the inactivation of pathways controlled by the tumour suppressor p53. Here, we show for the first time that HPV38 alters p53 functions. Expression of HPV38 E6 and E7 in human keratinocytes or in the skin of transgenic mice induces stabilization of wild-type p53. This selectively activates the transcription of deltaNp73, an isoform of the p53-related protein p73, which in turn inhibits the capacity of p53 to induce the transcription of genes involved in growth suppression and apoptosis. DeltaNp73 downregulation by an antisense oligonucleotide leads to transcriptional re-activation of p53-regulated genes and apoptosis. Our findings illustrate a novel mechanism of the alteration of p53 function that is mediated by a cutaneous HPV type and support the role of HPV38 and deltaNp73 in human carcinogenesis.
authors.affiliation: Infections & Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France.
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.forename: Anouk
authors.initials: A
authors.lastname: Smet
authors.forename: Rutao
authors.initials: R
authors.lastname: Cui
authors.forename: Agnes
authors.initials: A
authors.lastname: Hautefeuille
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gabet
authors.forename: Bakary S
authors.initials: BS
authors.lastname: Sylla
authors.forename: Lutz
authors.initials: L
authors.lastname: Gissmann
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000821:virology*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D050725:Papillomavirus E7 Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human