title: Early Steps of Jaagsiekte Sheep Retrovirus-Mediated Cell Transformation Involve the Interaction between Env and the RALBP1 Cellular Protein.
abstract: Ovine pulmonary adenocarcinoma is a naturally occurring lung cancer in sheep induced by the Jaagsiekte sheep retrovirus (JSRV). Its envelope glycoprotein (Env) carries oncogenic properties, and its expression is sufficient to induce in vitro cell transformation and in vivo lung adenocarcinoma. The identification of cellular partners of the JSRV envelope remains crucial for deciphering mechanisms leading to cell transformation. We initially identified RALBP1 (RalA binding protein 1; also known as RLIP76 or RIP), a cellular protein implicated in the ras pathway, as a partner of JSRV Env by yeast two-hybrid screening and confirmed formation of RALBP1/Env complexes in mammalian cells. Expression of the RALBP1 protein was repressed in tumoral lungs and in tumor-derived alveolar type II cells. Through its inhibition using specific small interfering RNA (siRNA), we showed that RALBP1 was involved in envelope-induced cell transformation and in modulation of the mTOR (mammalian target of rapamycin)/p70S6K pathway by the retroviral envelope.
  
  
  OBJECTIVE
  JSRV-induced lung adenocarcinoma is of importance for the sheep industry. While the envelope has been reported as the oncogenic determinant of the virus, the cellular proteins directly interacting with Env are still not known. Our report on the formation of RALBP/Env complexes and the role of this interaction in cell transformation opens up a new hypothesis for the dysregulation observed upon virus infection in sheep.
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Monot
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Erny
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gineys
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Desloire
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Dolmazon
authors.affiliation: CIRI U1111, UMR5308, INSERM, CNRS, Université Lyon 1, ENS de Lyon, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Aublin-Gex
authors.affiliation: CIRI U1111, UMR5308, INSERM, CNRS, Université Lyon 1, ENS de Lyon, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Archer
authors.affiliation: Université de Lyon, Université Lyon 1, INRA, UMR754, Retrovirus and Comparative Pathology, UMS 3444, SFR BioSciences, Lyon, France caroline.leroux@univ-lyon1.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Leroux
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002472:Cell Transformation, Viral / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D015686:Gene Products, env / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D022141:Jaagsiekte sheep retrovirus / Q000502:physiology*; D046912:Multiprotein Complexes / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D011648:Pulmonary Adenomatosis, Ovine / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics; D012756:Sheep; D012757:Sheep Diseases / Q000503:physiopathology* / Q000821:virology*; D018709:Statistics, Nonparametric; D020798:Two-Hybrid System Techniques
chemical_list: D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D020690:GTPase-Activating Proteins; D015686:Gene Products, env; D046912:Multiprotein Complexes; C095637:RALBP1 protein, human; D034741:RNA, Small Interfering