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Artículo

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

Camporeale, GabrielaIcon ; Lorenzo, Juan R.; Thomas, Maria GabrielaIcon ; Salvatierra, Edgardo; Borkosky, Silvia SusanaIcon ; Risso, Marikena GuadalupeIcon ; Sánchez Miguel, Ignacio EnriqueIcon ; de Prat Gay, GonzaloIcon ; Alonso, Leonardo GabrielIcon
Fecha de publicación: 11/2016
Editorial: Elsevier B.V.
Revista: Redox Biology
ISSN: 2213-2317
e-ISSN: 2213-2317
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Virología; Bioquímica y Biología Molecular

Resumen

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
Palabras clave: Transforming Protein Ros-Sensing , Reactive Cysteine Acquisition Through Evolution , Redox-Switching Mechanism , Papillomavirus-Induced Cancers
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/29271
URL: http://www.sciencedirect.com/science/article/pii/S2213231716301975
DOI: https://doi.org/10.1016/j.redox.2016.10.020
Colecciones
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Citación
Camporeale, Gabriela; Lorenzo, Juan R.; Thomas, Maria Gabriela; Salvatierra, Edgardo; Borkosky, Silvia Susana; et al.; Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein; Elsevier B.V.; Redox Biology; 11; 11-2016; 38-50
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