title: Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression.
abstract: Hypoxia has been associated with several pathological conditions ranging from stroke to cancer. This condition results in the activation of autophagy, a cyto-protective response involving the formation of double-membraned structures, the autophagosomes, in the cytoplasm. In this study, we investigated the cellular mechanisms regulating the autophagy gene Ambra1, after exposure to a hypoxia mimetic, cobalt chloride (CoCl2). We observed that, upon CoCl2 administration, activation of the apoptotic machinery was concomitant with down-regulation of the pro-autophagic factor Ambra1, without affecting transcription. Additionally, co-treating the cells with the caspase inhibitor z-VAD-FMK did not restore Ambra1 protein levels, this implying the involvement of other regulatory mechanisms. Partial re-localization of Ambra1 mRNA to non-translating fractions and cytoplasmic P-bodies was further detected. Thus, in this pseudohypoxic context, Ambra1 mRNA translocation to P-bodies and translational suppression correlated with increased cell death.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Pourpirali
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valacca
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Merlo
authors.affiliation: Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Rizza
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: D'Amico
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy; Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017209:Apoptosis; D001343:Autophagy; D015687:Cell Hypoxia; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis; D034443:RNA Transport; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
chemical_list: C553334:AMBRA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger