Role of elongin-binding domain of von Hippel Lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a key mediator of angiogenesis for both physiological and pathological conditions. It is well established that the hypoxic induction of VPF/VEGF is in large part an increase in the stability of its mRNA. A Hu family ubiquitously ...
expressed RNA-binding protein HuR has recently been shown to be important for VPF/VEGF mRNA stabilization. In renal cancer cells, the inactivation of the tumor suppressor protein von Hippel Lindau (VHL) leads to an increase in VPF/VEGF expression. VHL not only inhibits the transcription of VPF/VEGF but also plays a significant role in decreasing its mRNA stability. Here we delineate a possible mechanism by which VHL can control the function of HuR in order to regulate the stability of VPF/VEGF mRNA. The experiments presented here suggest that the association of the elongin-binding domain of VHL with a specific RNA-binding domain of HuR (RRM1) is important for the destabilizing function of VHL on VPF/VEGF mRNA.
Mesh Terms:
Carcinoma, Renal Cell, Humans, Kidney Neoplasms, Neovascularization, Pathologic, RNA Stability, Transcription Factors, Tumor Cells, Cultured, Vascular Endothelial Growth Factors, Von Hippel-Lindau Tumor Suppressor Protein
Oncogene
Date: Nov. 24, 2005
Download Curated Data For This Publication
142748
Switch View:
  • Interactions 3