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The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase.
Sciacovelli, Marco; Guzzo, Giulia; Morello, Virginia; Frezza, Christian; Zheng, Liang; Nannini, Nazarena; Calabrese, Fiorella; Laudiero, Gabriella; Esposito, Franca; Landriscina, Matteo; Defilippi, Paola; Bernardi, Paolo; Rasola, Andrea.
Afiliación
  • Sciacovelli M; CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy.
  • Guzzo G; CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy.
  • Morello V; Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, University of Torino, 10125 Torino, Italy.
  • Frezza C; Cancer Research United Kingdom, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
  • Zheng L; Cancer Research United Kingdom, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G61 1BD, UK.
  • Nannini N; Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, 35121 Padova, Italy.
  • Calabrese F; Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, 35121 Padova, Italy.
  • Laudiero G; Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy.
  • Esposito F; Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy.
  • Landriscina M; Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
  • Defilippi P; Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, University of Torino, 10125 Torino, Italy.
  • Bernardi P; CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy. Electronic address: bernardi@bio.unipd.it.
  • Rasola A; CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy. Electronic address: rasola@bio.unipd.it.
Cell Metab ; 17(6): 988-999, 2013 Jun 04.
Article en En | MEDLINE | ID: mdl-23747254
We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Succinato Deshidrogenasa / Proteínas HSP90 de Choque Térmico / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2013 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Succinato Deshidrogenasa / Proteínas HSP90 de Choque Térmico / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2013 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos