PIAS4 SUMOylates VHL at lysine-159, lysine-171, and lysine-196 with SUMO1 (Cai et al. 2010, Cai and Robertson 2010, Chien et al. 2013). SUMOylation facilitates the oligomerization of VHL, abolishes the inhibitory function of VHL on HIF1A, and abolishes the tumor suppressor function of VHL by inactivating the ubiquitinylation activity of VHL.
SUMO transferase activity of PIAS4 [nucleoplasm]