Mostrar el registro sencillo del ítem
dc.contributor.author
Celegato, Marta
dc.contributor.author
Messa, Lorenzo
dc.contributor.author
Goracci, Laura
dc.contributor.author
Mercorelli, Beatrice
dc.contributor.author
Bertagnin, Chiara
dc.contributor.author
Spyrakis, Francesca
dc.contributor.author
Suarez, Irina Paula
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Cousido Siah, Alexandra
dc.contributor.author
Travé, Gilles
dc.contributor.author
Banks, Lawrence
dc.contributor.author
Cruciani, Gabriele
dc.contributor.author
Palù, Giorgio
dc.contributor.author
Loregian, Arianna
dc.date.available
2022-04-05T12:25:51Z
dc.date.issued
2020-02
dc.identifier.citation
Celegato, Marta; Messa, Lorenzo; Goracci, Laura; Mercorelli, Beatrice; Bertagnin, Chiara; et al.; A novel small-molecule inhibitor of the human papillomavirus E6-p53 interaction that reactivates p53 function and blocks cancer cells growth; Elsevier Ireland; Cancer Letters; 470; 2-2020; 115-125
dc.identifier.issn
0304-3835
dc.identifier.uri
http://hdl.handle.net/11336/154356
dc.description.abstract
Despite prophylactic vaccination campaigns, human papillomavirus (HPV)-induced cancers still represent a major medical issue for global population, thus specific anti-HPV drugs are needed. Since the ability of HPV E6 oncoprotein to promote p53 degradation is linked to tumor progression, E6 has been proposed as an ideal target for cancer treatment. Using the crystal structure of the E6/E6AP/p53 complex, we performed an in silico screening of small-molecule libraries against a highly conserved alpha-helix in the N-terminal domain of E6 involved in the E6-p53 interaction. We discovered a compound able to inhibit the E6-mediated degradation of p53 through disruption of E6-p53 binding both in vitro and in cells. This compound could restore p53 intracellular levels and transcriptional activity, reduce the viability and proliferation of HPV-positive cancer cells, and block 3D cervospheres formation. Mechanistic studies revealed that the compound anti-tumor activity mainly relies on induction of cell cycle arrest and senescence. Our data demonstrate that the disruption of the direct E6-p53 interaction can be obtained with a small-molecule compound leading to specific antitumoral activity in HPV-positive cancer cells and thus represents a new approach for anti-HPV drug development.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Ireland
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
HUMAN PAPILLOMAVIRUS
dc.subject
E6 ONCOPROTEIN
dc.subject
P53
dc.subject
SMALL-MOLECULE INHIBITORS
dc.subject.classification
Virología
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
A novel small-molecule inhibitor of the human papillomavirus E6-p53 interaction that reactivates p53 function and blocks cancer cells growth
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-09-06T21:05:46Z
dc.journal.volume
470
dc.journal.pagination
115-125
dc.journal.pais
Irlanda
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.description.fil
Fil: Celegato, Marta. Università di Padova; Italia
dc.description.fil
Fil: Messa, Lorenzo. Università di Padova; Italia
dc.description.fil
Fil: Goracci, Laura. Università di Perugia; Italia
dc.description.fil
Fil: Mercorelli, Beatrice. Università di Padova; Italia
dc.description.fil
Fil: Bertagnin, Chiara. Università di Padova; Italia
dc.description.fil
Fil: Spyrakis, Francesca. Università di Torino; Italia
dc.description.fil
Fil: Suarez, Irina Paula. Centre National de la Recherche Scientifique. Igbmc; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Cousido Siah, Alexandra. Centre National de la Recherche Scientifique. Igbmc; Francia
dc.description.fil
Fil: Travé, Gilles. Centre National de la Recherche Scientifique. Igbmc; Francia
dc.description.fil
Fil: Banks, Lawrence. International Centre for Genetic Engineering and Biotechnology; Italia
dc.description.fil
Fil: Cruciani, Gabriele. Università di Perugia; Italia
dc.description.fil
Fil: Palù, Giorgio. Università di Padova; Italia
dc.description.fil
Fil: Loregian, Arianna. Università di Padova; Italia
dc.journal.title
Cancer Letters
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.canlet.2019.10.046
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S030438351930549X
Archivos asociados