Role of elongin-binding domain of von Hippel Lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma.
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.
Datta
Kaustubh
K
Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic Foundation, Rochester, MN 55905, USA.
Mondal
Susanta
S
Sinha
Sutapa
S
Li
Jinping
J
Wang
Enfeng
E
Knebelmann
Bertrand
B
Karumanchi
S Ananth
SA
Mukhopadhyay
Debabrata
D
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000503:physiopathology; D000075065:Elongin; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D020871:RNA Stability; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000502:physiology*
D000075065:Elongin; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein