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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

Oncogene volume 24, pages 7850–7858 (2005)Cite this article

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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Author notes

  1. Kaustubh Datta, Susanta Mondal, S Ananth Karumanchi and Debabrata Mukhopadhyay: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic Foundation, Rochester, MN, USA

    Kaustubh Datta, Sutapa Sinha, Jinping Li, Enfeng Wang & Debabrata Mukhopadhyay

  2. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Susanta Mondal & S Ananth Karumanchi

  3. Hopital Necker, Paris, France

    Bertrand Knebelmann

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  1. Kaustubh Datta
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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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