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

39 Citations (Scopus)

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
StatePublished - Nov 24 2005

Fingerprint

RNA Stability
Renal Cell Carcinoma
Vascular Endothelial Growth Factor A
Genes
elongin
Messenger RNA
Von Hippel-Lindau Tumor Suppressor Protein
Physiologic Neovascularization
Pathologic Neovascularization
RNA-Binding Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Role of elongin-binding domain of von hippel lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma. / Datta, Kaustubh; Mondal, Susanta; Sinha, Sutapa; Li, Jinping; Wang, Enfeng; Knebelmann, Bertrand; Karumanchi, S. Ananth; Mukhopadhyay, Debabrata.

In: Oncogene, Vol. 24, No. 53, 24.11.2005, p. 7850-7858.

Research output: Contribution to journalArticle

Datta, K, Mondal, S, Sinha, S, Li, J, Wang, E, Knebelmann, B, Karumanchi, SA & Mukhopadhyay, D 2005, 'Role of elongin-binding domain of von hippel lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma', Oncogene, vol. 24, no. 53, pp. 7850-7858. https://doi.org/10.1038/sj.onc.1208912
Datta, Kaustubh ; Mondal, Susanta ; Sinha, Sutapa ; Li, Jinping ; Wang, Enfeng ; Knebelmann, Bertrand ; Karumanchi, S. Ananth ; Mukhopadhyay, Debabrata. / Role of elongin-binding domain of von hippel lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma. In: Oncogene. 2005 ; Vol. 24, No. 53. pp. 7850-7858.
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