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Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Author

Listed:
  • Christian Frezza

    (Cancer Research UK, Beatson Institute for Cancer Research)

  • Liang Zheng

    (Cancer Research UK, Beatson Institute for Cancer Research)

  • Ori Folger

    (The Blavatnik School of Computer Science, Tel Aviv University)

  • Kartik N. Rajagopalan

    (University of Texas–Southwestern Medical Center at Dallas)

  • Elaine D. MacKenzie

    (Cancer Research UK, Beatson Institute for Cancer Research)

  • Livnat Jerby

    (The Blavatnik School of Computer Science, Tel Aviv University)

  • Massimo Micaroni

    (The University of Queensland, Institute for Molecular Bioscience, St Lucia)

  • Barbara Chaneton

    (Cancer Research UK, Beatson Institute for Cancer Research)

  • Julie Adam

    (Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive)

  • Ann Hedley

    (Cancer Research UK, Beatson Institute for Cancer Research)

  • Gabriela Kalna

    (Cancer Research UK, Beatson Institute for Cancer Research)

  • Ian P. M. Tomlinson

    (Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Patrick J. Pollard

    (Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive)

  • Dave G. Watson

    (Strathclyde Institute of Pharmaceutical and Biomedical Sciences, University of Strathclyde)

  • Ralph J. Deberardinis

    (University of Texas–Southwestern Medical Center at Dallas)

  • Tomer Shlomi

    (Technion, Israel Institute of Technology)

  • Eytan Ruppin

    (The Blavatnik School of Computer Science, Tel Aviv University
    The Sackler School of Medicine, Tel Aviv University)

  • Eyal Gottlieb

    (Cancer Research UK, Beatson Institute for Cancer Research)

Abstract

Drug targets for kidney cancer Inherited mutations in fumarate hydratase (FH), an enzyme in the tricarboxylic acid cycle — which links many of the metabolic reactions in aerobic cellular respiration — can lead to malignancies including kidney cancer. Frezza et al. now observe a metabolic pathway in FH-deficient cells that converts glutamine into bilirubin through the synthesis and degradation of haem. This renders FH-deficient cells sensitive to inhibition of haem oxygenase, a key enzyme in this pathway. Haem oxygenase might therefore be a therapeutic target in patients with tumours associated with FH loss.

Suggested Citation

  • Christian Frezza & Liang Zheng & Ori Folger & Kartik N. Rajagopalan & Elaine D. MacKenzie & Livnat Jerby & Massimo Micaroni & Barbara Chaneton & Julie Adam & Ann Hedley & Gabriela Kalna & Ian P. M. To, 2011. "Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase," Nature, Nature, vol. 477(7363), pages 225-228, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7363:d:10.1038_nature10363
    DOI: 10.1038/nature10363
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    Cited by:

    1. André Schultz & Amina A Qutub, 2016. "Reconstruction of Tissue-Specific Metabolic Networks Using CORDA," PLOS Computational Biology, Public Library of Science, vol. 12(3), pages 1-33, March.
    2. Héctor García Martín & Vinay Satish Kumar & Daniel Weaver & Amit Ghosh & Victor Chubukov & Aindrila Mukhopadhyay & Adam Arkin & Jay D Keasling, 2015. "A Method to Constrain Genome-Scale Models with 13C Labeling Data," PLOS Computational Biology, Public Library of Science, vol. 11(9), pages 1-34, September.
    3. William R Harcombe & Nigel F Delaney & Nicholas Leiby & Niels Klitgord & Christopher J Marx, 2013. "The Ability of Flux Balance Analysis to Predict Evolution of Central Metabolism Scales with the Initial Distance to the Optimum," PLOS Computational Biology, Public Library of Science, vol. 9(6), pages 1-11, June.
    4. Marlous Kamp & Jakub Surmacki & Marc Segarra Mondejar & Tim Young & Karolina Chrabaszcz & Fadwa Joud & Vincent Zecchini & Alyson Speed & Christian Frezza & Sarah E. Bohndiek, 2024. "Raman micro-spectroscopy reveals the spatial distribution of fumarate in cells and tissues," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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