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

Kaustubh Datta, Susanta Mondal, Sutapa Sinha, Jinping Li, Enfeng Wang, Bertrand Knebelmann, S. Ananth Karumanchi, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7850-7858
Number of pages9
JournalOncogene
Volume24
Issue number53
DOIs
Publication statusPublished - Nov 24 2005

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Keywords

  • Angiogenesis
  • Renal cell carcinoma
  • VHL, HuR
  • VPF
  • VPF/VEGF
  • mRNA stability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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