Sabine Hacot
University of Lyon
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Publication
Featured researches published by Sabine Hacot.
Cancer Cell | 2013
Virginie Marcel; Sandra E. Ghayad; Stéphane Belin; Gabriel Thérizols; Anne Pierre Morel; Eduardo Solano-Gonzàlez; Julie A. Vendrell; Sabine Hacot; Hichem C. Mertani; Marie Alexandra Albaret; Jean-Christophe Bourdon; Lee Jordan; Alastair M. Thompson; Yasmine Tafer; Rong Cong; Philippe Bouvet; Jean Christophe Saurin; Frédéric Catez; Anne Catherine Prats; Alain Puisieux; Jean Jacques Diaz
Summary Ribosomes are specialized entities that participate in regulation of gene expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivated in p53-inactivated cancer cells, although involvement of p53 on ribosome quality is unknown. Here, we show that p53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied by modifications of the rRNA methylation pattern, impairment of translational fidelity, and an increase of internal ribosome entry site (IRES)-dependent translation initiation of key cancer genes. FBL overexpression contributes to tumorigenesis and is associated with poor survival in patients with breast cancer. Thus, p53 acts as a safeguard of protein synthesis by regulating FBL and the subsequent quality and intrinsic activity of ribosomes.
Journal of Virology | 2012
Anna Greco; Loredana Arata; Eric Soler; Xavier Gaume; Yohann Couté; Sabine Hacot; Aleth Callé; Karine Monier; Alberto L. Epstein; Jean-Charles Sanchez; Philippe Bouvet; Jean-Jacques Diaz
ABSTRACT Herpes simplex virus type 1 (HSV-1) infection induces profound nucleolar modifications at the functional and organizational levels, including nucleolar invasion by several viral proteins. One of these proteins is US11, which exhibits several different functions and displays both cytoplasmic localization and clear nucleolar localization very similar to that of the major multifunctional nucleolar protein nucleolin. To determine whether US11 interacts with nucleolin, we purified US11 protein partners by coimmunoprecipitations using a tagged protein, Flag-US11. From extracts of cells expressing Flag-US11 protein, we copurified a protein of about 100 kDa that was further identified as nucleolin. In vitro studies have demonstrated that nucleolin interacts with US11 and that the C-terminal domain of US11, which is required for US11 nucleolar accumulation, is sufficient for interaction with nucleolin. This association was confirmed in HSV-1-infected cells. We found an increase in the nucleolar accumulation of US11 in nucleolin-depleted cells, thereby revealing that nucleolin could play a role in US11 nucleocytoplasmic trafficking through one-way directional transport out of the nucleolus. Since nucleolin is required for HSV-1 nuclear egress, the interaction of US11 with nucleolin may participate in the outcome of infection.
Journal of Virology | 2004
Stéphane Giraud; Chantal Diaz-Latoud; Sabine Hacot; Julien Textoris; Roland P. Bourette; Jean-Jacques Diaz
ABSTRACT Homeodomain-interacting protein kinase 2 (HIPK2) is a nuclear serine/threonine kinase of the subfamily of dual-specificity Yak1-related kinase proteins. HIPK2 was first described as a homeodomain-interacting protein kinase acting as a corepressor for homeodomain transcription factors. More recently, it was reported that HIPK2 plays a role in p53-mediated cellular apoptosis and could also participate in the regulation of the cell cycle. US11 protein of herpes simplex virus type 1 is a multifunctional protein involved in the regulation of several processes related to the survival of cells submitted to environmental stresses by mechanisms that are not fully elucidated. In an attempt to better understand the multiple functions of US11, we identified cellular binding partners of this protein by using the yeast two-hybrid system. We report that US11 interacts with HIPK2 through the PEST domain of HIPK2 and that this interaction occurs also in human cells. This interaction modifies the subcellular distribution of HIPK2 and protects the cell against the HIPK2-induced cell growth arrest.
Science Signaling | 2012
Céline Delloye-Bourgeois; David Goldschneider; Andrea Paradisi; Gabriel Therizols; Stéphane Belin; Sabine Hacot; Manuel Rosa-Calatrava; Jean-Yves Scoazec; Jean-Jacques Diaz; Agnès Bernet; Patrick Mehlen
A nuclear-localized isoform of netrin may enhance ribosome biogenesis to promote cancer growth. Nucleolar Netrin Ribosomes are the cellular sites for protein synthesis, and ribosomal RNA is transcribed in nuclear structures called nucleoli. The higher proliferation rate of tumor cells requires an increased rate of protein synthesis, and enhancing the rates of ribosomal RNA transcription and the production of ribosomes confers a growth advantage. Delloye-Bourgeois et al. characterized a truncated isoform of netrin-1 called ΔN-netrin-1 that, unlike the full-length form, was not secreted but instead localized to nucleoli where it interacted with proteins involved in ribosomal RNA transcription. Overexpression of ΔN-netrin-1 increased the cytoplasmic pool of ribosomes, proliferation of cultured cells, and tumor growth in an in vivo model. ΔN-netrin-1 was also detected in some cancer cell lines and human cancers. The current antitumor agents targeting the full-length netrin-1 isoform cannot enter cells and, thus, would likely not affect the pro-tumor activity of nucleolar ΔN-netrin-1. Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, ΔN-netrin-1 was targeted to the nucleolus, where it interacted with nucleolar proteins, affected nucleolar ultrastructure, and interacted with the promoters of ribosomal genes. Moreover, ΔN-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo. Thus, some cancer cells produce not only a full-length, secreted form of netrin-1 that promotes cell survival but also a truncated netrin-1 that stimulates cell proliferation, potentially by enhancing ribosome biogenesis.
Current protocols in pharmacology | 2010
Stephane Belin; Sabine Hacot; Lionel Daudignon; Gabriel Therizols; Stéphane Pourpe; Hichem C. Mertani; Manuel Rosa-Calatrava; Jean-Jacques Diaz
Highly conserved during evolution, the ribosome is the central effector of protein synthesis. In mammalian cells, the ribosome is a macromolecular complex composed of four different ribosomal RNAs (rRNA) and about 80 ribosomal proteins. Requiring more than 200 factors, ribosome biogenesis is a highly complex process that takes place mainly within the nucleoli of eukaryotic cells. Crystallographic data suggest that the ribosome is a ribozyme, in which the rRNA catalyses the peptide bond formation and ensures quality control of the translation. Ribosomal proteins are involved in this molecular mechanism; nonetheless, their role is still not fully characterized. Recent studies suggest that ribosomes themselves and/or the mechanisms underlying their synthesis, processing, and assembly play a key role in the establishment and progression of several human pathologies. The protocol described here is simple, efficient, and robust, and allows one to purify high‐quality ribosomes from human cultured cell lines. Ribosomes purified with this protocol are adequate for most of the subsequent analyses of their RNA and protein content. Curr. Protoc. Cell Biol. 49:3.40.1‐3.40.11.
RNA | 2010
Stéphane Belin; Karine Kindbeiter; Sabine Hacot; Marie Alexandra Albaret; Jean-Xavier Roca-Martinez; Gabriel Thérizols; Olivier Grosso; Jean-Jacques Diaz
The ribosome is the central effector of protein synthesis, and its synthesis is intimately coordinated with that of proteins. At present, the most documented way to modulate ribosome biogenesis involves control of rDNA transcription by RNA polymerase I (RNA Pol I). Here we show that after infection of human cells with herpes simplex virus type 1 (HSV-1) the rate of ribosome biogenesis is modulated independently of RNA Pol I activity by a dramatic change in the rRNA maturation pathway. This process permits control of the ribosome biogenesis rate, giving the possibility of escaping ribosomal stress and eventually allowing assembly of specialized kinds of ribosomes.
Current protocols in pharmacology | 2010
Sabine Hacot; Yohann Couté; Stéphane Belin; Marie Alexandra Albaret; Hichem C. Mertani; Jean-Charles Sanchez; Manuel Rosa-Calatrava; Jean-Jacques Diaz
Nucleoli are now recognized as multi‐functional nuclear domains involved in several fundamental cell processes such as ribosome biogenesis, regulation of the assembly of non‐ribosomal ribonucleoprotein complexes, tRNA maturation, sequestration of protein, viral infection, and cellular ageing. Extensive proteomic analyses of these nucleolar domains after their purification have contributed to the description of their multiple biological functions. Because nucleoli are the largest and densest nuclear structures, they are easily amenable to purification from nuclei of cultured animal cells using the protocol described in this unit. Curr. Protoc. Cell Biol. 47:3.36.1‐3.36.10.
Scientific Reports | 2016
Olivier Terrier; Coralie Carron; Benoît de Chassey; Julia Dubois; Aurélien Traversier; Thomas Julien; Gaëlle Cartet; Anaïs Proust; Sabine Hacot; Denis Ressnikoff; Vincent Lotteau; Bruno Lina; Jean-Jacques Diaz; Vincent Moules; Manuel Rosa-Calatrava
Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.
Annales D Endocrinologie | 2008
J-J Diaz; Christophe Couderc; Yohann Couté; Gilles Poncet; S. Pourpe; Sabine Hacot; Françoise Borson-Chazot; K. Aguerra; J.Y. Scoazec; Jean-Charles Sanchez; Catherine Roche
J.-J. Diaz a,∗, C. Couderc b, Y. Couté c, G. Poncet b, S. Pourpe a, S. Hacot a, F. Borson-Chazot d, K. Aguerra a, J.-Y. Scoazec b, J.-C. Sanchez c, C. Roche b a Université de Lyon, Université Lyon 1, CNRS, UMR 5534, Centre de Génétique Moléculaire et Cellulaire, Villeurbanne, France b Inserm, U865, IFR Lyon-Est, Université de Lyon, Université Lyon 1, Lyon, France c Département de biologie structurale et bioinformatique, Biomedical Proteomics Research Group, centre médical universitaire, Genève, Suisse iversi
International Journal of Biological Macromolecules | 2017
Wannapa Sornjai; Pathrapol Lithanatudom; Jenny Erales; Philippe Joly; Alain Francina; Sabine Hacot; Suthat Fucharoen; Saovaros Svasti; Jean Jacques Diaz; Hichem C. Mertani; Duncan R. Smith