VEGF is a critical mediator of hypoxia-induced angiogenesis in numerous physiological and pathophysiological conditions. The hypoxic induction of VEGF is due in large part to an increase in the stability of its mRNA. We recently demonstrated that the stabilization of VEGF mRNA by hypoxia is dependent upon the RNA-binding protein HuR. This report describes the identification of a 40-bp functional HuR binding site in the VEGF mRNA 3'-untranslated region. This element can confer HuR-mediated stabilization of a heterologous gene in vitro and in vivo. Furthermore, the element is sufficient to confer an increase in the hypoxic induction of a heterologous gene. Deletion of the HuR binding site within this 40-bp element as mapped by RNase T1 and lead footprinting uncouples a stabilizing sequence from a destabilizing sequence, thus providing a novel RNA-protein regulatory model that might be exploited to manipulate VEGF expression and hypoxia-induced angiogenesis.
机构:Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Ford, LP
;
Watson, J
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机构:Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Watson, J
;
Keene, JD
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机构:Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Keene, JD
;
Wilusz, J
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Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
机构:
Mem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA
Joseph, B
;
Orlian, M
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Mem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA
Orlian, M
;
Furneaux, H
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Mem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA
机构:Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Ford, LP
;
Watson, J
论文数: 0引用数: 0
h-index: 0
机构:Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Watson, J
;
Keene, JD
论文数: 0引用数: 0
h-index: 0
机构:Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
Keene, JD
;
Wilusz, J
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h-index: 0
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
机构:
Mem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA
Joseph, B
;
Orlian, M
论文数: 0引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA
Orlian, M
;
Furneaux, H
论文数: 0引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Mol Neurooncol Lab, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA