Review Article

Familial Renal Cancer: Molecular Genetics and Surgical Management

Figure 4

In a normoxic environment, HIF is hydroxylated by HPH allowing the VHL complex to initiate ubiquitin-mediated breakdown in the proteosome. In HLRCC, FH alteration results in a buildup of fumarate. Fumarate competitively inhibits HPH allowing a rise in HIF levels and subsequent transcription of downstream genes. (From Pfaffenroth and Linehan [59], with permission.)
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