دورية أكاديمية

Human papillomavirus 16 oncoprotein E7 stimulates UBF1-mediated rDNA gene transcription, inhibiting a p53-independent activity of p14ARF.

التفاصيل البيبلوغرافية
العنوان: Human papillomavirus 16 oncoprotein E7 stimulates UBF1-mediated rDNA gene transcription, inhibiting a p53-independent activity of p14ARF.
المؤلفون: Dichamp I; Unité de Virologie, Centre Hospitalier Universitaire de Poitiers, Faculté de Médecine et Pharmacie, Poitiers, France., Séité P; Equipe Emergente 2RCT «Récepteurs, Régulations, Cellules Tumorales», Université de Poitiers, Poitiers, France., Agius G; Unité de Virologie, Centre Hospitalier Universitaire de Poitiers, Faculté de Médecine et Pharmacie, Poitiers, France., Barbarin A; Equipe Emergente 2RCT «Récepteurs, Régulations, Cellules Tumorales», Université de Poitiers, Poitiers, France., Beby-Defaux A; Unité de Virologie, Centre Hospitalier Universitaire de Poitiers, Faculté de Médecine et Pharmacie, Poitiers, France; Equipe Emergente 2RCT «Récepteurs, Régulations, Cellules Tumorales», Université de Poitiers, Poitiers, France.
المصدر: PloS one [PLoS One] 2014 May 05; Vol. 9 (5), pp. e96136. Date of Electronic Publication: 2014 May 05 (Print Publication: 2014).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Cell Transformation, Viral* , Transcription, Genetic*, DNA, Ribosomal/*metabolism , Human papillomavirus 16/*metabolism , Papillomavirus E7 Proteins/*metabolism , Pol1 Transcription Initiation Complex Proteins/*metabolism , Tumor Suppressor Protein p14ARF/*metabolism, Amino Acid Substitution ; Animals ; Cell Line, Tumor ; Cell Nucleolus ; DNA, Ribosomal/genetics ; Female ; Human papillomavirus 16/genetics ; Humans ; Mice ; Mutation, Missense ; Papillomavirus E7 Proteins/genetics ; Pol1 Transcription Initiation Complex Proteins/genetics ; Tumor Suppressor Protein p14ARF/genetics
مستخلص: High-risk human papillomavirus oncoproteins E6 and E7 play a major role in HPV-related cancers. One of the main functions of E7 is the degradation of pRb, while E6 promotes the degradation of p53, inactivating the p14ARF-p53 pathway. pRb and p14ARF can repress ribosomal DNA (rDNA) transcription in part by targeting the Upstream Binding Factor 1 (UBF1), a key factor in the activation of RNA polymerase I machinery. We showed, through ectopic expression and siRNA silencing of p14ARF and/or E7, that E7 stimulates UBF1-mediated rDNA gene transcription, partly because of increased levels of phosphorylated UBF1, preventing the inhibitory function of p14ARF. Unexpectedly, activation of rDNA gene transcription was higher in cells co-expressing p14ARF and E7, compared to cells expressing E7 alone. We did not find a difference in P-UBF1 levels that could explain this data. However, p14ARF expression induced E7 to accumulate into the nucleolus, where rDNA transcription takes place, providing an opportunity for E7 to interact with nucleolar proteins involved in this process. GST-pull down and co-immunoprecipitation assays showed interactions between p14ARF, UBF1 and E7, although p14ARF and E7 are not able to directly interact. Co-expression of a pRb-binding-deficient mutant (E7C24G) and p14ARF resulted in EC24G nucleolar accumulation, but not in a significant higher activation of rDNA transcription, suggesting that the inactivation of pRb is involved in this phenomenon. Thus, p14ARF fails to prevent E7-mediated UBF1 phosphorylation, but could facilitate nucleolar pRb inactivation by targeting E7 to the nucleolus. While others have reported that p19ARF, the mouse homologue of p14ARF, inhibits some functions of E7, we showed that E7 inhibits a p53-independent function of p14ARF. These results point to a mutually functional interaction between p14ARF and E7 that might partly explain why the sustained p14ARF expression observed in most cervical pre-malignant lesions and malignancies may be ineffective.
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المشرفين على المادة: 0 (DNA, Ribosomal)
0 (Papillomavirus E7 Proteins)
0 (Pol1 Transcription Initiation Complex Proteins)
0 (Tumor Suppressor Protein p14ARF)
0 (oncogene protein E7, Human papillomavirus type 16)
0 (transcription factor UBF)
تواريخ الأحداث: Date Created: 20140507 Date Completed: 20150612 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4010441
DOI: 10.1371/journal.pone.0096136
PMID: 24798431
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0096136