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HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells.
Sánchez-Quiles V., Mora M. I., Segura V., Greco A., Epstein A. L. et al
Mol Cell Proteomics 10, 6 (2011) M111.009126 - http://hal.archives-ouvertes.fr/hal-00709868
Sciences du Vivant/Biochimie, Biologie Moléculaire
HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells.
Virginia Sánchez-Quiles1, María I Mora1, 2, Victor Segura1, Anna Greco3, Alberto L Epstein3, Maria Giovanna Foschini, Loïc Dayon4, Jean-Charles Sanchez4, Jesús Prieto5, 6, Fernando J Corrales1, Enrique Santamaría1
1 :  Proteomics
Center for Applied Medical Research (CIMA)
Espagne
2 :  SUBATECH - Laboratoire SUBATECH Nantes
http://www-subatech.in2p3.fr/
CNRS : UMR6457 – IN2P3 – Université de Nantes – École Nationale Supérieure des Mines - Nantes
4, rue Alfred Kastler - 44070 Nantes Cedex 03
France
3 :  CGphiMC - Centre de génétique et de physiologie moléculaire et cellulaire
http://cgphimc.univ-lyon1.fr/
CNRS : UMR5534 – Université Claude Bernard - Lyon I (UCBL)
UNIVERSITE CLAUDE BERNARD LYON 1 Bâtiment Gregor Mendel 16 rue Raphaël Dubois 69622 VILLEURBANNE CEDEX
France
4 :  BPRG - Biomedical Proteomics Research Group
http://expasy.org/people/bprg/
Centre médical universitaire
Département de Biologie Structurale et Bioinformatique, 1 Rue Michel Servet, 1211 Geneva 4
Suisse
5 :  CIMA - Division of Hepatology and Gene Therapy
http://www.aipgene.org/partners/cima.html
Center for Applied Medical Research
Pamplona
Espagne
6 :  CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
https://www.ciberehd.org/
Liver Unit, Clínica Universitaria, CIBER-EHD
C/ Córcega 180 bajos dcha. 08036 Barcelona
Espagne
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.
Anglais

Mol Cell Proteomics
internationale
Articles dans des revues avec comité de lecture
06/2011
05/04/2011
10
6
M111.009126

Algorithms – Cell Adhesion Molecules – Cell Line – Tumor – Cell Nucleus – Cyclin-Dependent Kinase Inhibitor p27 – Cyclin-Dependent Kinase Inhibitor p57 – Cytoplasm – Herpes Simplex – Herpesvirus 1 – Human – Humans – Protein Isoforms – Protein Transport – RNA Interference – RNA-Binding Proteins – Statistics – Nonparametric – Tandem Mass Spectrometry – Two-Dimensional Difference Gel Electrophoresis – Viral Plaque Assay – Viral Proteins