title: An eIF4E-interacting peptide induces cell death in cancer cell lines.
abstract: The eukaryotic initiation factor eIF4E is essential for cap-dependent initiation of translation in eukaryotes. Abnormal regulation of eIF4E has been implicated in oncogenic transformation. We developed an eIF4E-binding peptide derived from Angel1, a partner of eIF4E that we recently identified. We show here that this peptide fused to a penetratin motif causes drastic and rapid cell death in several epithelial cancer cell lines. This necrotic cell death was characterized by a drop in ATP levels with F-actin network injury being a key step in extensive plasma membrane blebbing and membrane permeabilization. This synthetic eIF4E-binding peptide provides a candidate pharmacophore for a promising new cancer therapy strategy.
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [2] CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] Université Européenne de Bretagne, Brittany, France.
authors.forename: M
authors.initials: M
authors.lastname: Masse
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [2] CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] Université Européenne de Bretagne, Brittany, France.
authors.forename: V
authors.initials: V
authors.lastname: Glippa
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [2] CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] Université Européenne de Bretagne, Brittany, France [4] Institut de Cancéro-hématologie, Département d'Hématologie, Hôpital Morvan, CHRU, Brest, France.
authors.forename: H
authors.initials: H
authors.lastname: Saad
authors.affiliation: 1] Université Européenne de Bretagne, Brittany, France [2] Institut de Cancéro-hématologie, Département d'Hématologie, Hôpital Morvan, CHRU, Brest, France.
authors.forename: R
authors.initials: R
authors.lastname: Le Bloas
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [2] CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] Université Européenne de Bretagne, Brittany, France.
authors.forename: I
authors.initials: I
authors.lastname: Gauffeny
authors.affiliation: 1] Université Européenne de Bretagne, Brittany, France [2] Institut de Cancéro-hématologie, Département d'Hématologie, Hôpital Morvan, CHRU, Brest, France.
authors.forename: C
authors.initials: C
authors.lastname: Berthou
authors.affiliation: 1] Université Européenne de Bretagne, Brittany, France [2] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Végétaux marins et biomolécules, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] CNRS, UMR 8227, Integrative Biology of Marine Models, Végétaux marins et biomolécules, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Czjzek
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [2] CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] Université Européenne de Bretagne, Brittany, France.
authors.forename: P
authors.initials: P
authors.lastname: Cormier
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [2] CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, Roscoff cedex, France [3] Université Européenne de Bretagne, Brittany, France.
authors.forename: B
authors.initials: B
authors.lastname: Cosson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D021961:Cell Membrane Structures / Q000187:drug effects / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D009336:Necrosis; D009369:Neoplasms / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D011817:Rabbits
chemical_list: D000199:Actins; D039561:Eukaryotic Initiation Factor-4E; D010455:Peptides