30-40 nM siRNA

The transcription factor HIF-1alpha is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1alpha is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1alpha homeostasis. Loss of Cezanne decreases HIF-1alpha target gene expression due to a reduction in HIF-1alpha protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1alpha depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1alpha protein stability and that loss of Cezanne stimulates HIF-1alpha degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy.