title: Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells.
abstract: Enoxacin is a small molecule that stimulates RNA interference (RNAi) and acts as a growth inhibitor selectively in cancer but not in untransformed cells. Here, we used alkenox, a clickable enoxacin surrogate, coupled with quantitative mass spectrometry, to identify PIWIL3 as a mechanistic target of enoxacin. PIWIL3 is an Argonaute protein of the PIWI subfamily that is mainly expressed in the germline and that mediates RNAi through piRNAs. Our results suggest that cancer cells re-express PIWIL3 to repress RNAi through miRNAs and thus open a new opportunity for cancer-specific targeting.
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin , 2500 Speedway, Austin, Texas 78712, United States.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Abell
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin , 2500 Speedway, Austin, Texas 78712, United States.
authors.forename: Marvin
authors.initials: M
authors.lastname: Mercado
authors.affiliation: UPR2301, Institut de Chimie des Substances Naturelles , 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.|Organic Synthesis and Cell Biology Group, Institut Curie, PSL Research University , 26 rue d'Ulm, 75248 Paris Cedex 05, France.|CNRS UMR3666 , 75005 Paris, France.|INSERM U1143 , 75005 Paris, France.
authors.forename: Tatiana
authors.identifier: 0000-0002-1110-0643
authors.initials: T
authors.lastname: Cañeque
authors.affiliation: UPR2301, Institut de Chimie des Substances Naturelles , 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.|Organic Synthesis and Cell Biology Group, Institut Curie, PSL Research University , 26 rue d'Ulm, 75248 Paris Cedex 05, France.|CNRS UMR3666 , 75005 Paris, France.|INSERM U1143 , 75005 Paris, France.
authors.forename: Raphaël
authors.identifier: 0000-0001-7668-446X
authors.initials: R
authors.lastname: Rodriguez
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin , 2500 Speedway, Austin, Texas 78712, United States.
authors.forename: Blerta
authors.identifier: 0000-0002-0517-9607
authors.initials: B
authors.lastname: Xhemalce
mesh_terms: D060565:Argonaute Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015365:Enoxacin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D015394:Molecular Structure
chemical_list: D060565:Argonaute Proteins; C556794:PIWIL3 protein, human; D015365:Enoxacin