Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein

Infection with oncogenic human papillomavirus induces deregulation of cellular redox homeostasis. Virus replication and papillomavirus-induced cell transformation require persistent expression of viral oncoproteins E7 and E6 that must retain their functionality in a persistent oxidative environment....

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Autores principales:	Thomas, María Gabriela, Salvatierra Colussi, Edgardo Enrique, de Prat Gay, Gonzalo
Publicado:	2017
Materias:	cysteine protein E7 reactive oxygen metabolite disulfide oncogene protein E7, Human papillomavirus type 16 Article carboxy terminal sequence cell nucleus controlled study cytoplasm disulfide bond genetic conservation Human papillomavirus type 11 Human papillomavirus type 16 Human papillomavirus type 18 molecular evolution nonhuman oxidation reduction reaction phylogeny priority journal sequence analysis transport at the cellular level cell transformation genetics metabolism neoplasm nucleolus oxidative stress pathology protein transport virus replication Cell Nucleolus Cell Transformation, Neoplastic Cysteine Cytoplasm Disulfides Neoplasms Oxidation-Reduction Oxidative Stress Papillomavirus E7 Proteins Protein Transport Virus Replication
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22132317_v11_n_p38_Camporeale http://hdl.handle.net/20.500.12110/paper_22132317_v11_n_p38_Camporeale
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_22132317_v11_n_p38_Camporeale
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spelling	paper:paper_22132317_v11_n_p38_Camporeale2023-06-08T16:35:17Z Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein Thomas, María Gabriela Salvatierra Colussi, Edgardo Enrique de Prat Gay, Gonzalo cysteine protein E7 reactive oxygen metabolite cysteine disulfide oncogene protein E7, Human papillomavirus type 16 protein E7 Article carboxy terminal sequence cell nucleus controlled study cytoplasm disulfide bond genetic conservation Human papillomavirus type 11 Human papillomavirus type 16 Human papillomavirus type 18 molecular evolution nonhuman oxidation reduction reaction phylogeny priority journal sequence analysis transport at the cellular level cell transformation genetics metabolism neoplasm nucleolus oxidation reduction reaction oxidative stress pathology protein transport virus replication Cell Nucleolus Cell Transformation, Neoplastic Cysteine Cytoplasm Disulfides Neoplasms Oxidation-Reduction Oxidative Stress Papillomavirus E7 Proteins Protein Transport Virus Replication Infection with oncogenic human papillomavirus induces deregulation of cellular redox homeostasis. Virus replication and papillomavirus-induced cell transformation require persistent expression of viral oncoproteins E7 and E6 that must retain their functionality in a persistent oxidative environment. Here, we dissected the molecular mechanisms by which E7 oncoprotein can sense and manage the potentially harmful oxidative environment of the papillomavirus-infected cell. The carboxy terminal domain of E7 protein from most of the 79 papillomavirus viral types of alpha genus, which encloses all the tumorigenic viral types, is a cysteine rich domain that contains two classes of cysteines: strictly conserved low reactive Zn+2 binding and degenerate reactive cysteine residues that can sense reactive oxygen species (ROS). Based on experimental data obtained from E7 proteins from the prototypical viral types 16, 18 and 11, we identified a couple of low pKa nucleophilic cysteines that can form a disulfide bridge upon the exposure to ROS and regulate the cytoplasm to nucleus transport. From sequence analysis and phylogenetic reconstruction of redox sensing states we propose that reactive cysteine acquisition through evolution leads to three separate E7s protein families that differ in the ROS sensing mechanism: non ROS-sensitive E7s; ROS-sensitive E7s using only a single or multiple reactive cysteine sensing mechanisms and ROS-sensitive E7s using a reactive-resolutive cysteine couple sensing mechanism. © 2016 The Authors Fil:Thomas, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Salvatierra, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:de Prat Gay, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22132317_v11_n_p38_Camporeale http://hdl.handle.net/20.500.12110/paper_22132317_v11_n_p38_Camporeale
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	cysteine protein E7 reactive oxygen metabolite cysteine disulfide oncogene protein E7, Human papillomavirus type 16 protein E7 Article carboxy terminal sequence cell nucleus controlled study cytoplasm disulfide bond genetic conservation Human papillomavirus type 11 Human papillomavirus type 16 Human papillomavirus type 18 molecular evolution nonhuman oxidation reduction reaction phylogeny priority journal sequence analysis transport at the cellular level cell transformation genetics metabolism neoplasm nucleolus oxidation reduction reaction oxidative stress pathology protein transport virus replication Cell Nucleolus Cell Transformation, Neoplastic Cysteine Cytoplasm Disulfides Neoplasms Oxidation-Reduction Oxidative Stress Papillomavirus E7 Proteins Protein Transport Virus Replication
spellingShingle	cysteine protein E7 reactive oxygen metabolite cysteine disulfide oncogene protein E7, Human papillomavirus type 16 protein E7 Article carboxy terminal sequence cell nucleus controlled study cytoplasm disulfide bond genetic conservation Human papillomavirus type 11 Human papillomavirus type 16 Human papillomavirus type 18 molecular evolution nonhuman oxidation reduction reaction phylogeny priority journal sequence analysis transport at the cellular level cell transformation genetics metabolism neoplasm nucleolus oxidation reduction reaction oxidative stress pathology protein transport virus replication Cell Nucleolus Cell Transformation, Neoplastic Cysteine Cytoplasm Disulfides Neoplasms Oxidation-Reduction Oxidative Stress Papillomavirus E7 Proteins Protein Transport Virus Replication Thomas, María Gabriela Salvatierra Colussi, Edgardo Enrique de Prat Gay, Gonzalo Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
topic_facet	cysteine protein E7 reactive oxygen metabolite cysteine disulfide oncogene protein E7, Human papillomavirus type 16 protein E7 Article carboxy terminal sequence cell nucleus controlled study cytoplasm disulfide bond genetic conservation Human papillomavirus type 11 Human papillomavirus type 16 Human papillomavirus type 18 molecular evolution nonhuman oxidation reduction reaction phylogeny priority journal sequence analysis transport at the cellular level cell transformation genetics metabolism neoplasm nucleolus oxidation reduction reaction oxidative stress pathology protein transport virus replication Cell Nucleolus Cell Transformation, Neoplastic Cysteine Cytoplasm Disulfides Neoplasms Oxidation-Reduction Oxidative Stress Papillomavirus E7 Proteins Protein Transport Virus Replication
description	Infection with oncogenic human papillomavirus induces deregulation of cellular redox homeostasis. Virus replication and papillomavirus-induced cell transformation require persistent expression of viral oncoproteins E7 and E6 that must retain their functionality in a persistent oxidative environment. Here, we dissected the molecular mechanisms by which E7 oncoprotein can sense and manage the potentially harmful oxidative environment of the papillomavirus-infected cell. The carboxy terminal domain of E7 protein from most of the 79 papillomavirus viral types of alpha genus, which encloses all the tumorigenic viral types, is a cysteine rich domain that contains two classes of cysteines: strictly conserved low reactive Zn+2 binding and degenerate reactive cysteine residues that can sense reactive oxygen species (ROS). Based on experimental data obtained from E7 proteins from the prototypical viral types 16, 18 and 11, we identified a couple of low pKa nucleophilic cysteines that can form a disulfide bridge upon the exposure to ROS and regulate the cytoplasm to nucleus transport. From sequence analysis and phylogenetic reconstruction of redox sensing states we propose that reactive cysteine acquisition through evolution leads to three separate E7s protein families that differ in the ROS sensing mechanism: non ROS-sensitive E7s; ROS-sensitive E7s using only a single or multiple reactive cysteine sensing mechanisms and ROS-sensitive E7s using a reactive-resolutive cysteine couple sensing mechanism. © 2016 The Authors
author	Thomas, María Gabriela Salvatierra Colussi, Edgardo Enrique de Prat Gay, Gonzalo
author_facet	Thomas, María Gabriela Salvatierra Colussi, Edgardo Enrique de Prat Gay, Gonzalo
author_sort	Thomas, María Gabriela
title	Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
title_short	Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
title_full	Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
title_fullStr	Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
title_full_unstemmed	Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
title_sort	degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus e7 oncoprotein
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22132317_v11_n_p38_Camporeale http://hdl.handle.net/20.500.12110/paper_22132317_v11_n_p38_Camporeale
work_keys_str_mv	AT thomasmariagabriela degeneratecysteinepatternsmediatetworedoxsensingmechanismsinthepapillomaviruse7oncoprotein AT salvatierracolussiedgardoenrique degeneratecysteinepatternsmediatetworedoxsensingmechanismsinthepapillomaviruse7oncoprotein AT depratgaygonzalo degeneratecysteinepatternsmediatetworedoxsensingmechanismsinthepapillomaviruse7oncoprotein
_version_	1768544202227974144

Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein

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