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

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.

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Acknowledgements

This work was partly supported by NIH Grants CA78383 and HL70567 and also by a grant from the American Cancer Society to DM. SAK was supported by a KO8 award (DK 02825 from NIH).

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Correspondence to Debabrata Mukhopadhyay.

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Datta, K., Mondal, S., Sinha, S. et al. Role of elongin-binding domain of von hippel lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma. Oncogene 24, 7850–7858 (2005). https://doi.org/10.1038/sj.onc.1208912

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Keywords

  • VPF
  • VPF/VEGF
  • mRNA stability
  • angiogenesis
  • renal cell carcinoma
  • VHL, HuR

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