title: Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release.
abstract: Eukaryotic translation initiation factor 4E (eIF4E) markedly reduces cellular susceptibility to apoptosis. However, the mechanism by which the translation apparatus operates on the cellular apoptotic machinery remains uncertain. Here we show that eIF4E-mediated rescue from Myc-dependent apoptosis is accompanied by inhibition of mitochondrial cytochrome c release. Experiments achieving gain and loss of function demonstrate that eIF4E-mediated rescue is governed by pretranslational and translational activation of bcl-x as well as by additional intermediates acting directly on, or upstream of, the mitochondria. Thus, our data trace a pathway controlling apoptotic susceptibility that begins with the activity state of the protein synthesis machinery and leads to interdiction of the apoptotic program at the mitochondrial checkpoint.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Shunan
authors.initials: S
authors.lastname: Li
authors.forename: Tasaburo
authors.initials: T
authors.lastname: Takasu
authors.forename: David M
authors.initials: DM
authors.lastname: Perlman
authors.forename: Mark S
authors.initials: MS
authors.lastname: Peterson
authors.forename: David
authors.initials: D
authors.lastname: Burrichter
authors.forename: Svetlana
authors.initials: S
authors.lastname: Avdulov
authors.forename: Peter B
authors.initials: PB
authors.lastname: Bitterman
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Polunovsky
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism*; D017931:DNA Primers; D004622:Embryo, Mammalian; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D016259:Genes, myc; D007700:Kinetics; D008928:Mitochondria / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic; D051020:bcl-X Protein
chemical_list: C494813:Bcl2l1 protein, rat; D003574:Cytochrome c Group; D017931:DNA Primers; D039561:Eukaryotic Initiation Factor-4E; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases