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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Datta, K; Mondal, S; Sinha, S; Li, J; Wang, E; Knebelmann, B; Karumanchi, SA; Mukhopadhyay, D

Published Date

  • November 24, 2005

Published In

Volume / Issue

  • 24 / 53

Start / End Page

  • 7850 - 7858

PubMed ID

  • 16170373

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1208912


  • eng

Conference Location

  • England