Negative regulation of hypoxia inducible factor-1α by necdin

Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that mediates cellular and systemic homeostatic responses to reduce O2 availability, such as erythropoiesis, angiogenesis, and glycolysis. Using the yeast two-hybrid screening system, we found that the oxygen dependent degradation (ODD) domain of HIF-1α interacts with necdin, a growth suppressor. The interaction of necdin with HIF-1α was confirmed using coimmunoprecipitation with the overexpressed HIF-1α. Biological effect of necdin on HIF-1α showed that necdin reduces the transcriptional activity of HIF-1 under hypoxia. Moreover, necdin decreased the level of the HIF-1α protein, but not that of mRNA, implying a possibility of necdin-mediated HIF-1α degradation. Furthermore, necdin has an anti-angiogenic activity in the tube formation assay and CAM assay, which might be due to the downregulation of HIF-1α. Collectively, these results suggest that necdin can be a novel negative regulator of HIF-1α stability via the direct interaction.