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CULLIN 2 (CUL2) is a component of the ElonginB/C-CUL2-RBX-1-Von Hippel-Lindau (VHL) tumor suppressor complex that ubiquitinates and degrades hypoxia-inducible factor α (HIFα). HIFα is a transcription factor that mediates the expression of hypoxia-sensitive genes, including vascular endothelial growth factor (VEGF), which in turn regulates vasculogenesis. Whereas CUL2 participates in the degradation of HIFα, the potential role of CUL2 in the regulation of other cellular processes is less well established. In the present study, suppression of CUL2 expression by Cul2 siRNA inhibited HIFα transcriptional activation of the VEGF gene in vitro, indicating that CUL2 plays a role distinct from its known function in HIFα degradation. Because ARNT heterodimerizes with HIFα, we assessed whether CUL2 influenced ARNT expression. Cul2 siRNA inhibited the expression of endogenous ARNT. Ectopically expressed …