658767.fig.002a
(a)
658767.fig.002b
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658767.fig.002c
(c)
Figure 2: The VHL complex targets HIF-1α and HIF-2α for ubiquitin-mediated degradation. In clear cell RCC, an alteration in the VHL gene in the α or β domain disrupts HIF degradation. HIF overaccumulates leading to increased transcription of downstream genes. (a) VHL alteration; (b) VHL/HIF pathway molecular targeting; and (c) VHL/HIF downstream molecular targeting. (From Linehan and Zbar [23], with permission.)