publication . Other literature type . Preprint . Article . 2017

Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells

Gonçalves, Emanuel; Sciacovelli, Marco; Costa, Ana SH; Tran, Maxine Gia Binh; Johnson, Timothy Isaac; Machado, Daniel; Frezza, Christian; Saez-Rodriguez, Julio;
English
  • Published: 13 Jun 2017
  • Publisher: RWTH Aachen University
Abstract
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 ...
Subjects
free text keywords: Science & Technology, Cell Line, Tumor, Humans, Neoplasms, Fumarate Hydratase, Pyruvate Dehydrogenase (Lipoamide), Neoplasm Proteins, Protein Processing, Post-Translational, Phosphoproteomics, Cancer cell, Genetics, Fumarase, Phosphorylation, Proteomics, Cell biology, Signal transduction, Pyruvate dehydrogenase complex, Post-translational regulation, Biology, Biotechnology, Applied Microbiology and Biotechnology, Bioengineering, Biochemistry, Citric acid cycle, Article, Metabolism, Cancer, Modelling, Cancer, Metabolism, Modelling, Phosphoproteomics
46 references, page 1 of 4

Beltrao, P., Albanèse, V., Kenner, L.R., Swaney, D.L., Burlingame, A., Villén, J., Lim, W.A., Fraser, J.S., Frydman, J., Krogan, N.J., 2012. Systematic functional prioritization of protein posttranslational modifications. Cell 150, 413-425. [OpenAIRE]

Casado, P., Rodriguez-Prados, J.-C., Cosulich, S.C., Guichard, S., Vanhaesebroeck, B., Joel, S., Cutillas, P.R., 2013. Kinase-substrate enrichment analysis provides insights into the heterogeneity of signaling pathway activation in leukemia cells. Sci. Signal. 6, rs6.

der Walt, S. van, Colbert, S.C., Varoquaux, G., 2011. The NumPy array: a structure for efficient numerical computation. Comput. Sci. Eng. 13, 22-30.

Dinkel, H., Chica, C., Via, A., Gould, C.M., Jensen, L.J., Gibson, T.J., Diella, F., 2011. Phospho.ELM: a database of phosphorylation sites-update 2011. Nucleic Acids Res. 39, D261-D267.

Duarte, N.C., Becker, S.A., Jamshidi, N., Thiele, I., Mo, M.L., Vo, T.D., Srivas, R., Palsson, B.Ø., 2007. Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc. Natl. Acad. Sci. USA 104, 1777-1782.

Frezza, C., Zheng, L., Folger, O., Rajagopalan, K.N., MacKenzie, E.D., Jerby, L., Micaroni, M., Chaneton, B., Adam, J., Hedley, A., Kalna, G., Tomlinson, I.P.M., Pollard, P.J., Watson, D.G., Deberardinis, R.J., Shlomi, T., Ruppin, E., Gottlieb, E., 2011. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477, 225-228. [OpenAIRE]

Gaude, E., Frezza, C., 2016. Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Nat. Commun. 7, 13041. [OpenAIRE]

Gonçalves, E., Raguz Nakic, Z., Zampieri, M., Wagih, O., Ochoa, D., Sauer, U., Beltrao, P., Saez-Rodriguez, J., 2017. Systematic analysis of transcriptional and post-transcriptional regulation of metabolism in yeast. PLoS Comput. Biol. 13, e1005297. [OpenAIRE]

Grant, C.M., 2008. Metabolic reconfiguration is a regulated response to oxidative stress. J. Biol. 7, 1.

Hanahan, D., Weinberg, R.A., 2011. Hallmarks of cancer: the next generation. Cell 144, 646-674.

Hanahan, D., Weinberg, R.A., 2000. The hallmarks of cancer. Cell 100, 57-70.

Hornbeck, P.V., Zhang, B., Murray, B., Kornhauser, J.M., Latham, V., Skrzypek, E., 2015. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 43, D512-D520.

Hu, J., Locasale, J.W., Bielas, J.H., O'Sullivan, J., Sheahan, K., Cantley, L.C., Vander Heiden, M.G., Vitkup, D., 2013. Heterogeneity of tumor-induced gene expression changes in the human metabolic network. Nat. Biotechnol. 31, 522-529. [OpenAIRE]

Hunter, J.D., 2007. Matplotlib: a 2D graphics environment. Comput. Sci. Eng. 9, 90-95.

Isaacs, J.S., Jung, Y.J., Mole, D.R., Lee, S., Torres-Cabala, C., Chung, Y.-L., Merino, M., Trepel, J., Zbar, B., Toro, J., Ratcliffe, P.J., Linehan, W.M., Neckers, L., 2005. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8, 143-153.

46 references, page 1 of 4
Abstract
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 ...
Subjects
free text keywords: Science & Technology, Cell Line, Tumor, Humans, Neoplasms, Fumarate Hydratase, Pyruvate Dehydrogenase (Lipoamide), Neoplasm Proteins, Protein Processing, Post-Translational, Phosphoproteomics, Cancer cell, Genetics, Fumarase, Phosphorylation, Proteomics, Cell biology, Signal transduction, Pyruvate dehydrogenase complex, Post-translational regulation, Biology, Biotechnology, Applied Microbiology and Biotechnology, Bioengineering, Biochemistry, Citric acid cycle, Article, Metabolism, Cancer, Modelling, Cancer, Metabolism, Modelling, Phosphoproteomics
46 references, page 1 of 4

Beltrao, P., Albanèse, V., Kenner, L.R., Swaney, D.L., Burlingame, A., Villén, J., Lim, W.A., Fraser, J.S., Frydman, J., Krogan, N.J., 2012. Systematic functional prioritization of protein posttranslational modifications. Cell 150, 413-425. [OpenAIRE]

Casado, P., Rodriguez-Prados, J.-C., Cosulich, S.C., Guichard, S., Vanhaesebroeck, B., Joel, S., Cutillas, P.R., 2013. Kinase-substrate enrichment analysis provides insights into the heterogeneity of signaling pathway activation in leukemia cells. Sci. Signal. 6, rs6.

der Walt, S. van, Colbert, S.C., Varoquaux, G., 2011. The NumPy array: a structure for efficient numerical computation. Comput. Sci. Eng. 13, 22-30.

Dinkel, H., Chica, C., Via, A., Gould, C.M., Jensen, L.J., Gibson, T.J., Diella, F., 2011. Phospho.ELM: a database of phosphorylation sites-update 2011. Nucleic Acids Res. 39, D261-D267.

Duarte, N.C., Becker, S.A., Jamshidi, N., Thiele, I., Mo, M.L., Vo, T.D., Srivas, R., Palsson, B.Ø., 2007. Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc. Natl. Acad. Sci. USA 104, 1777-1782.

Frezza, C., Zheng, L., Folger, O., Rajagopalan, K.N., MacKenzie, E.D., Jerby, L., Micaroni, M., Chaneton, B., Adam, J., Hedley, A., Kalna, G., Tomlinson, I.P.M., Pollard, P.J., Watson, D.G., Deberardinis, R.J., Shlomi, T., Ruppin, E., Gottlieb, E., 2011. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477, 225-228. [OpenAIRE]

Gaude, E., Frezza, C., 2016. Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Nat. Commun. 7, 13041. [OpenAIRE]

Gonçalves, E., Raguz Nakic, Z., Zampieri, M., Wagih, O., Ochoa, D., Sauer, U., Beltrao, P., Saez-Rodriguez, J., 2017. Systematic analysis of transcriptional and post-transcriptional regulation of metabolism in yeast. PLoS Comput. Biol. 13, e1005297. [OpenAIRE]

Grant, C.M., 2008. Metabolic reconfiguration is a regulated response to oxidative stress. J. Biol. 7, 1.

Hanahan, D., Weinberg, R.A., 2011. Hallmarks of cancer: the next generation. Cell 144, 646-674.

Hanahan, D., Weinberg, R.A., 2000. The hallmarks of cancer. Cell 100, 57-70.

Hornbeck, P.V., Zhang, B., Murray, B., Kornhauser, J.M., Latham, V., Skrzypek, E., 2015. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 43, D512-D520.

Hu, J., Locasale, J.W., Bielas, J.H., O'Sullivan, J., Sheahan, K., Cantley, L.C., Vander Heiden, M.G., Vitkup, D., 2013. Heterogeneity of tumor-induced gene expression changes in the human metabolic network. Nat. Biotechnol. 31, 522-529. [OpenAIRE]

Hunter, J.D., 2007. Matplotlib: a 2D graphics environment. Comput. Sci. Eng. 9, 90-95.

Isaacs, J.S., Jung, Y.J., Mole, D.R., Lee, S., Torres-Cabala, C., Chung, Y.-L., Merino, M., Trepel, J., Zbar, B., Toro, J., Ratcliffe, P.J., Linehan, W.M., Neckers, L., 2005. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8, 143-153.

46 references, page 1 of 4
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publication . Other literature type . Preprint . Article . 2017

Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells

Gonçalves, Emanuel; Sciacovelli, Marco; Costa, Ana SH; Tran, Maxine Gia Binh; Johnson, Timothy Isaac; Machado, Daniel; Frezza, Christian; Saez-Rodriguez, Julio;