Phosphorylation of the von Hippel-Lindau protein (VHL) by protein kinase CK2 reduces its protein stability and affects p53 and HIF-1α mediated transcription

By using 4,5,6,7-tetrabromobenzotriazole (TBB), a CK2-specific inhibitor, as well as a mutant VHL where serines 33, 38 and 43 were replaced by alanines we found that CK2 phosphorylation affected the VHL protein half-life and increased VHL protein stability. Further, we found that inhibition of VHL phosphorylation by CK2 reduced p53 function. In addition, the enhanced levels of VHL due to CK2 inhibition contributed to the down-regulation of HIF-activity and degradation of HIF-1α. Thus, these results demonstrate that phosphorylation of VHL by CK2 plays an important role in the regulation of VHL protein stability and may contribute to the survival of tumour cells.