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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells
Authors: Sanchez-Quiles, V. (Virginia)
Mora, M.I. (María I.)
Segura, V. (Víctor)
Grecco, A. (Ana)
Epstein, A.L. (Alberto L.)
Foschini, M.G. (María Giovanna)
Dayon, L. (Loïc)
Sánchez, J.C. (Jean-Charles)
Prieto, J. (Jesús)
Corrales, F.J. (Fernando José)
Santamaria, E. (Enrique)
Keywords: Cell Nucleus/metabolism
Cytoplasm/metabolism
Herpes Simplex/metabolism
Herpesvirus 1, Human/physiology
RNA-Binding Proteins/metabolism
Issue Date: 2011
Publisher: American Society for Biochemistry and Molecular Biology
Publisher version: http://www.mcponline.org/content/10/6/M111.009126
ISSN: 1535-9484
Citation: Sanchez-Quiles V, Mora MI, Segura V, Greco A, Epstein AL, Foschini MG, et al. HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells. Mol Cell Proteomics 2011 Jun;10(6):M111.009126.
Abstract
Herpesvirus type 1 (HSV-1) based oncolytic vectors arise as a promising therapeutic alternative for neoplastic diseases including hepatocellular carcinoma. However, the mechanisms mediating the host cell response to such treatments are not completely known. It is well established that HSV-1 infection induces functional and structural alterations in the nucleus of the host cell. In the present work, we have used gel-based and shotgun proteomic strategies to elucidate the signaling pathways impaired in the nucleus of human hepatoma cells (Huh7) upon HSV-1 Cgal(+) infection. Both approaches allowed the identification of differential proteins suggesting impairment of cell functions involved in many aspects of host-virus interaction such as transcription regulation, mRNA processing, and mRNA splicing. Based on our proteomic data and additional functional studies, cellular protein quaking content (QKI) increases 4 hours postinfection (hpi), when viral immediate-early genes such as ICP4 and ICP27 could be also detected. Depletion of QKI expression by small interfering RNA results in reduction of viral immediate-early protein levels, subsequent decrease in early and late viral protein content, and a reduction in the viral yield indicating that QKI directly interferes with viral replication. In particular, HSV-1 Cgal(+) induces a transient increase in quaking I-5 isoform (QKI-5) levels, in parallel with an enhancement of p27(Kip1) protein content. Moreover, immunofluorescence microscopy showed an early nuclear redistribution of QKI-5, shuttling from the nucleus to the cytosol and colocalizing with nectin-1 in cell to cell contact regions at 16-24 hpi. This evidence sheds new light on mechanisms mediating hepatoma cell response to HSV-1 vectors highlighting QKI as a central molecular mediator.
Permanent link: http://hdl.handle.net/10171/21552
Appears in Collections:DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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