PMID:30718813

Citation	Kulkarni, RA, Bak, DW, Wei, D, Bergholtz, SE, Briney, CA, Shrimp, JH, Alpsoy, A, Thorpe, AL, Bavari, AE, Crooks, DR, Levy, M, Florens, L, Washburn, MP, Frizzell, N, Dykhuizen, EC, Weerapana, E, Linehan, WM and Meier, JL (2019) A chemoproteomic portrait of the oncometabolite fumarate. Nat. Chem. Biol. 15:391-400
Abstract	Hereditary cancer disorders often provide an important window into novel mechanisms supporting tumor growth. Understanding these mechanisms thus represents a vital goal. Toward this goal, here we report a chemoproteomic map of fumarate, a covalent oncometabolite whose accumulation marks the genetic cancer syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). We applied a fumarate-competitive chemoproteomic probe in concert with LC-MS/MS to discover new cysteines sensitive to fumarate hydratase (FH) mutation in HLRCC cell models. Analysis of this dataset revealed an unexpected influence of local environment and pH on fumarate reactivity, and enabled the characterization of a novel FH-regulated cysteine residue that lies at a key protein-protein interface in the SWI-SNF tumor-suppressor complex. Our studies provide a powerful resource for understanding the covalent imprint of fumarate on the proteome and lay the foundation for future efforts to exploit this distinct aspect of oncometabolism for cancer diagnosis and therapy.
Links	PubMed PMC6430658 Online version:10.1038/s41589-018-0217-y
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FUMH	enables	GO:0004333: fumarate hydratase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:FUMH	involved_in	GO:0006106: fumarate metabolic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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