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Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4: Expression and hypoxic regulation

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Abstract

The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) is responsible for maintaining the cellular levels of fructose-2,6-bisphosphate which is a key regulator of glycolysis. Here we have studied the expression of PFKFB-4 isozyme in the DB-1 melanoma cells. An additional isoform of PFKFB-4 mRNA with 148 bases insert in the amino-terminal region at high constitutive levels was identified in these cells. The expression of this splice isoform as well as main isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was responsible to hypoxia and dimethyloxalylglycine, an inhibitor of HIF-1 α hydroxylase enzymes, suggesting that the hypoxia responsiveness of PFKFB-4 gene in these cells is regulated by HIF-1α protein. Hypoxic induction of PFKFB4 mRNA in the DB-1 melanoma cells correlates with the expression of PFKFB-3 and VEGF mRNA which are known as HIF-1 dependent genes. Thus, our results clearly demonstrated the existence of splice isoform of PFKFB-4 mRNA in the DB-1 melanoma cells and its overexpression under hypoxic conditions. (Mol Cell Biochem xxx: 277–234, 2005)

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Authors and Affiliations

  1. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 9 Leontovycha Street, Kyiv, 01601, Ukraine

    Oleksandr H. Minchenko, Iryna L. Opentanova & Dmytro O. Minchenko

  2. National Cancer Center Research Institute East, Kashiwa, Chiba, 277-8577, Japan

    Tsutomu Ogura & Hiroyasu Esumi

Authors
  1. Oleksandr H. Minchenko
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  2. Tsutomu Ogura
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  3. Iryna L. Opentanova
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  4. Dmytro O. Minchenko
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  5. Hiroyasu Esumi
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Correspondence to Oleksandr H. Minchenko.

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Minchenko, O.H., Ogura, T., Opentanova, I.L. et al. Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4: Expression and hypoxic regulation. Mol Cell Biochem 280, 227–234 (2005). https://doi.org/10.1007/s11010-005-8009-6

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  • DOI: https://doi.org/10.1007/s11010-005-8009-6

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