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https://hdl.handle.net/1822/50466
Título: | Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells |
Autor(es): | Gonçalves, Emanuel Sciacovelli, Marco Costa, Ana S. H. Tran, Maxine Gia Binh Johnson, Timothy Isaac Machado, Daniel Frezza, Christian Saez-Rodriguez, Julio |
Palavras-chave: | Metabolism Cancer Phosphoproteomics Modelling |
Data: | 2018 |
Editora: | Elsevier |
Revista: | Metabolic Engineering |
Citação: | Gonçalves, Emanuel; Sciacovelli, Marco; Costa, Ana S. H.; Tran, Maxine Gia Binh; Johnson, Timothy Isaac; Machado, Daniel; Frezza, Christian; Saez-Rodriguez, Julio, Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells. Metabolic Engineering, 45, 149-157, 2018 |
Resumo(s): | Deregulated signal transduction and energy metabolism are hallmarks of cancer and both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we showed that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells, restricting carbon entry from glucose to the tricarboxylic acid cycle. Moreover, we confirmed PDHA1 phosphorylation in human FH-deficient tumours. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers with potential clinical applications. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/50466 |
DOI: | 10.1016/j.ymben.2017.11.011 |
ISSN: | 1096-7176 |
e-ISSN: | 1096-7184 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_47361_1.pdf | 1,04 MB | Adobe PDF | Ver/Abrir |