Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.

Journal article

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a f...

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Authors: Frezza, C; Zheng, L; Folger, O; Rajagopalan, K; MacKenzie, E

• Publication status: Published
• Journal: Nature
• Volume: 477
• Issue: 7363
• Pages: 225-228
• Publication date: 2011-09-01
• DOI: 10.1038/nature10363
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Mutation; Genes, Tumor Suppressor; Cells, Cultured; Heme Oxygenase (Decyclizing); Skin Neoplasms; Computer Simulation; Bilirubin; Citric Acid Cycle; Cell Line; Mice; Heme; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Fumarates; Fumarate Hydratase; Uterine Neoplasms; Animals; Mitochondria; Genes, Lethal; Leiomyomatosis; NAD; Glutamine