Fumarate hydratase (FH) mutation is associated with hereditary type 2 papillary renal cell carcinoma. Recently, we as well as others found that nuclear factor (erythroid-derived 2)-like 2 (NRF2) activation is a dominant feature of FH mutation. We demonstrate that in hereditary type 2 papillary renal cell carcinoma, fumarate covalently modified KEAP1 and leads to its ubiquitination. Consequently, NRF2 become activated. This predicts that similar mode of NRF2 activation may also be present in other tissues with FH mutation; overexpression of NRF2 target genes in various FH mutated tissues support the prediction that NRF2 is activated in these tissues. Variation in NRF2 targets expression may account for phenotypic differences among tumors associated with FH mutation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1134. doi:1538-7445.AM2012-1134