Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance

Ilaria Moscetti, Anna Rita Bizzarri, Salvatore Cannistraro Biophysics and Nanoscience Centre, Department of Ecology and Biology, Università della Tuscia, Viterbo, Italy Abstract: p53 plays an important role in the safeguard of the genome but it is frequently downregulated mainly by E3 u...

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Autores principales:	Moscetti I, Bizzarri AR, Cannistraro S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	p53 COP1 AFM AFS SPR protein- protein interaction Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b25b83b5d0714378a52a9e11da1ba33e
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spelling	oai:doaj.org-article:b25b83b5d0714378a52a9e11da1ba33e2021-12-02T07:21:40ZImaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance1178-2013https://doaj.org/article/b25b83b5d0714378a52a9e11da1ba33e2018-01-01T00:00:00Zhttps://www.dovepress.com/imaging-and-kinetics-of-the-bimolecular-complex-formed-by-the-tumor-su-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ilaria Moscetti, Anna Rita Bizzarri, Salvatore Cannistraro Biophysics and Nanoscience Centre, Department of Ecology and Biology, Università della Tuscia, Viterbo, Italy Abstract: p53 plays an important role in the safeguard of the genome but it is frequently downregulated mainly by E3 ubiquitin ligases among which COP1 plays an important role. The overexpression of COP1 has been reported to occur in several tumors and may be indicative of its overall oncogenic effect, which in turn might be originated by a direct interaction of COP1 with p53. Such an interaction may constitute a rewarding target for anticancer drug design strategies; therefore, a deeper understanding of its underlying molecular mechanism and kinetics is needed. The formation of a single p53–COP1 bimolecular complex was visualized by atomic force microscopy imaging on a mica substrate. The kinetic characterization of the complex, performed by atomic force spectroscopy and surface plasmon resonance, provided a KD value of ~10-8 M and a relative long lifetime in the order of minutes, both at the single-molecule level and in bulk solution. The surprisingly high affinity value and low dissociation rate of the p53–COP1 bimolecular complex, which is even stronger than the p53–MDM2 complex, should be considered a benchmark for designing, development and optimization of suitable drugs able to antagonize the complex formation with the aim of preventing the inhibitory effect of COP1 on the p53 oncosuppressive function. Keywords: p53, COP1, AFM, AFS, SPR, protein–protein interaction Moscetti IBizzarri ARCannistraro SDove Medical Pressarticlep53COP1AFMAFSSPRprotein- protein interactionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 251-259 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	p53 COP1 AFM AFS SPR protein- protein interaction Medicine (General) R5-920
spellingShingle	p53 COP1 AFM AFS SPR protein- protein interaction Medicine (General) R5-920 Moscetti I Bizzarri AR Cannistraro S Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance
description	Ilaria Moscetti, Anna Rita Bizzarri, Salvatore Cannistraro Biophysics and Nanoscience Centre, Department of Ecology and Biology, Università della Tuscia, Viterbo, Italy Abstract: p53 plays an important role in the safeguard of the genome but it is frequently downregulated mainly by E3 ubiquitin ligases among which COP1 plays an important role. The overexpression of COP1 has been reported to occur in several tumors and may be indicative of its overall oncogenic effect, which in turn might be originated by a direct interaction of COP1 with p53. Such an interaction may constitute a rewarding target for anticancer drug design strategies; therefore, a deeper understanding of its underlying molecular mechanism and kinetics is needed. The formation of a single p53–COP1 bimolecular complex was visualized by atomic force microscopy imaging on a mica substrate. The kinetic characterization of the complex, performed by atomic force spectroscopy and surface plasmon resonance, provided a KD value of ~10-8 M and a relative long lifetime in the order of minutes, both at the single-molecule level and in bulk solution. The surprisingly high affinity value and low dissociation rate of the p53–COP1 bimolecular complex, which is even stronger than the p53–MDM2 complex, should be considered a benchmark for designing, development and optimization of suitable drugs able to antagonize the complex formation with the aim of preventing the inhibitory effect of COP1 on the p53 oncosuppressive function. Keywords: p53, COP1, AFM, AFS, SPR, protein–protein interaction
format	article
author	Moscetti I Bizzarri AR Cannistraro S
author_facet	Moscetti I Bizzarri AR Cannistraro S
author_sort	Moscetti I
title	Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance
title_short	Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance
title_full	Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance
title_fullStr	Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance
title_full_unstemmed	Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance
title_sort	imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase cop1 as studied by atomic force microscopy and surface plasmon resonance
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/b25b83b5d0714378a52a9e11da1ba33e
work_keys_str_mv	AT moscettii imagingandkineticsofthebimolecularcomplexformedbythetumorsuppressorp53withubiquitinligasecop1asstudiedbyatomicforcemicroscopyandsurfaceplasmonresonance AT bizzarriar imagingandkineticsofthebimolecularcomplexformedbythetumorsuppressorp53withubiquitinligasecop1asstudiedbyatomicforcemicroscopyandsurfaceplasmonresonance AT cannistraros imagingandkineticsofthebimolecularcomplexformedbythetumorsuppressorp53withubiquitinligasecop1asstudiedbyatomicforcemicroscopyandsurfaceplasmonresonance
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Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance

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