HPV-mediated inactivation of tumor suppressor p53

Travé, Gilles; Zanier, Katia

doi:10.1080/15384101.2016.1191257

Cited by 26 publications

(23 citation statements)

References 7 publications

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“…We further characterized the functional effects of alphapapillomaviruses in tumors by integrating external PCAWG datasets such as driver mutations, mutational signatures, structural variations, gene expression profiles and patient survival. In head and neck cancer, HPV-positive tumors exhibit an almost complete mutual exclusivity with mutations in known drivers like TP53, CDKN2A and TERT (q=1.73x10-5, q=1.73x10-5, q=0.012; multiple testing corrected for presented mutations and in EBV and HPV, DISCOVER 22 ) (Figure 3c), as reported previously 25 , which could be explained by a mutation independent inactivation of TP53 through the human papillomaviruses [28][29][30] . Analyzing the mutational signatures enriched in these cases, we identified mutational signatures 2 as enriched for alphapapillomavirus positive cases in head and neck cancers (q=0.02; FDR corrected Wilkoxon Rank Sum test; Figure 3d) 31 .…”

Section: Alphapapillomavirussupporting

confidence: 71%

The landscape of viral associations in human cancers

Zapatka

Borozan

Brewer

et al. 2018

Preprint

103

148

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Potential viral pathogens were systematically investigated in the whole-genome and transcriptome sequencing of 2,656 donors as part of the Pan-Cancer Analysis of Whole Genomes using a consensus approach integrating three independent pathogen detection pipelines. Viruses were detected in 382 genomic and 68 transcriptome data sets. We extensively searched and characterized numerous features of virus-positive cancers integrating various PCAWG datasets. We show the high prevalence of known tumor associated viruses such as EBV, HBV and several HPV types. Our systematic analysis revealed that HPV presence was significantly exclusive with well-known driver mutations in head/neck cancer. A strong association was observed between HPV infection and the APOBEC mutational signatures, suggesting the role of impaired mechanism of antiviral cellular defense as a driving force in the development of cervical, bladder and head neck carcinoma. Viral integration into the host genome was observed for HBV, HPV16, HPV18 and AAV2 and associated with a local increase in copy number variations. The recurrent viral integrations at the TERT promoter were coupled to high telomerase expression uncovering a further mechanism to activate this tumor driving process. High levels of endogenous retrovirus ERV1 expression is linked to worse survival outcome in kidney cancer.

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Section: Alphapapillomavirussupporting

confidence: 71%

The landscape of viral associations in human cancers

Zapatka

Borozan

Brewer

et al. 2018

Preprint

103

148

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“…The ligation junctions (residues (15)(16) and (37-38), respectively) were chosen in the regions of the sequence that remain unstructured in the known complex with nuclear coactivator binding domain (NCBD) of CBP, 2 therefore modification of Gln16 and Gln38 into pseudo-glutamines is unlikely to affect the properties of the synthetic TAD-p53.…”

Section: Resultsmentioning

confidence: 99%

“…11 Furthermore, cancer-inducing viruses can inactivate p53, for example, E6 protein of human papilloma virus (HPV) induces p53 degradation. 15 The protein p53 consists of five major domains, such as transactivation domain (TAD), proline-rich domain, DNA binding core domain, tetramerization domain and regulatory domain. 13 The N-terminal TAD is acidic, intrinsically disordered and responsible for binding to various transcription factors.…”

Section: Introductionmentioning

confidence: 99%

Chemical synthesis of transactivation domain (TAD) of tumor suppressor protein p53 by native chemical ligation of three peptide segments

et al. 2019

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Torbeev. Chemical synthesis of transactivation domain (TAD) of tumor suppressor protein p53 by native chemical ligation of three peptide segments. Tetrahedron, Elsevier, 2018, 75 (6), pp.Please cite this article as: Baral A, Asokan A, Bauer V, Kieffer B, Torbeev V, Chemical synthesis of transactivation domain (TAD) of tumor suppressor protein p53 by native chemical ligation of three peptide segments, Tetrahedron (2018), doi: https://doi.

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“…However, compared with the control group, p53 protein accumulated mainly in the nuclei of cells treated with CDV or DDP, which was possibly caused by the decrease in E6 protein expression. This is assumed because analysis of other complex structures of the p53 core showed that the E6-binding surface of p53 was available for interaction not only in ‘free’ p53 tetramers but also in p53 molecules bound to DNA or other cellular proteins (10). These results were consistent with the findings of western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells

Yang

Dai

Chen

et al. 2016

Experimental and Therapeutic Medicine

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In order to evaluate the potential application value of cidofovir (CDV) in the prevention of human papillomavirus (HPV) infection and treatment of cervical cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as a positive control. An MTT assay was used to analyze the effects of CDV and DDP on HeLa cell proliferation. In addition, clone formation assay and Giemsa staining were used to examine the extent of HeLa cell apoptosis caused by CDV and DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells following propidium iodide staining, while western blot analysis identified the expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing immunofluorescence technique was used to locate the subcellular position of p53 in HeLa cells. The results demonstrated that CDV and DDP inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Flow cytometry showed that CDV and DDP treatments resulted in cell arrest in the S-phase, and triggered programmed cell death. Furthermore, western blot analysis revealed that CDV and DDP inhibited E6 protein expression and activated p53 expression in HeLa cells. Finally, the immunofluorescence results indicated that CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and time-dependent manner, reduced the expression of E6 protein, and reinstated p53 protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be a potential cervical cancer therapeutic strategy.

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HPV-mediated inactivation of tumor suppressor p53

Cited by 26 publications

References 7 publications

The landscape of viral associations in human cancers

The landscape of viral associations in human cancers

Chemical synthesis of transactivation domain (TAD) of tumor suppressor protein p53 by native chemical ligation of three peptide segments

Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells

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