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.

• Authors: Kaustubh Datta, Susanta Mondal, Sutapa Sinha, Jinping Li, Enfeng Wang, Bertrand Knebelmann, S Ananth Karumanchi, Debabrata Mukhopadhyay
• Journal: Oncogene (Oncogene) Vol. 24 Issue 53 Pg. 7850-8 (Nov 24 2005) ISSN: 0950-9232 [Print] England
• PMID: 16170373 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Elongin
• Transcription Factors
• Vascular Endothelial Growth Factors
• Von Hippel-Lindau Tumor Suppressor Protein

Topics

• Carcinoma, Renal Cell (genetics, physiopathology)
• Elongin
• Humans
• Kidney Neoplasms (genetics, physiopathology)
• Neovascularization, Pathologic
• RNA Stability
• Transcription Factors (metabolism)
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factors (biosynthesis)
• Von Hippel-Lindau Tumor Suppressor Protein (physiology)