Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9
| Autor: | Patrick Mehlen, Chantal Thibert, Rémy Sadoul, Joanna Fombonne, Catherine Guix, Pierre-Antoine Bissey |
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| Přispěvatelé: | Puisieux, Alain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 2, Neurodégénérescence et plasticité, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by institutional grants from the Ligue Contre le Cancer, INCA, ANR, and IP ApoSys., Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Grenoble Institut des Neurosciences ( GIN ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) |
| Rok vydání: | 2012 |
| Předmět: |
MESH : Cell Line
endocrine system diseases Apoptosis NEDD4 [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Dependence receptor MESH : Ubiquitination 0302 clinical medicine Ubiquitin [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] MESH: Caspase 3 MESH : Caspase 3 ComputingMilieux_MISCELLANEOUS Caspase-9 0303 health sciences Multidisciplinary biology Caspase 3 MESH: Real-Time Polymerase Chain Reaction Signal transducing adaptor protein Biological Sciences MESH : Mutagenesis Site-Directed Ubiquitin ligase MESH: Mutagenesis Site-Directed 030220 oncology & carcinogenesis Patched MESH : Real-Time Polymerase Chain Reaction [SDV.CAN]Life Sciences [q-bio]/Cancer macromolecular substances Real-Time Polymerase Chain Reaction MESH: Two-Hybrid System Techniques Cell Line 03 medical and health sciences Two-Hybrid System Techniques signalisation [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology 030304 developmental biology posttranslational modification MESH: Humans MESH: Apoptosis MESH : Humans Ubiquitination [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis protease MESH: Cell Line [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis MESH : Two-Hybrid System Techniques Mutagenesis Site-Directed biology.protein Cancer research MESH: Ubiquitination MESH : Apoptosis |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (26), pp.10510-5. ⟨10.1073/pnas.1200094109⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2012, 109 (26), pp.10510-10515. ⟨10.1073/pnas.1200094109⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2012, 109 (26), pp.10510-5. ⟨10.1073/pnas.1200094109⟩ Proceedings-National Academy of Sciences Usa Proceedings-National Academy of Sciences Usa, 2012, 109 (26), pp.10510-5. 〈10.1073/pnas.1200094109〉 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1200094109 |
| Popis: | International audience; Patched (Ptc), the main receptor for Sonic Hedgehog, is a tumor suppressor. Ptc has been shown to be a dependence receptor, and as such triggers apoptosis in the absence of its ligand. This apoptosis induction occurs through the recruitment by the Ptc intracellular domain of a caspase-activating complex, which includes the adaptor proteins DRAL and TUCAN, and the apical caspase-9. We show here that this caspase-activating complex also includes the E3 ubiquitin ligase NEDD4. We demonstrate that Ptc-mediated apoptosis and Ptc-induced caspase-9 activation require NEDD4. We show that Ptc, but not Bax, the prototypical inducer of the intrinsic cell-death pathway, triggers polyubiquitination of caspase-9. Moreover, a caspase-9 mutant that could not be ubiquitinated failed to mediate Ptc-induced apoptosis. Taken together, these data support the view that the Ptc dependence receptor specifically allows the activation of caspase-9 via its ubiquitination, which occurs via the recruitment by Ptc of NEDD4. |
| Databáze: | OpenAIRE |
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