UNIQUE ALTERNATIVE SPLICE VARIANTS OF MOUS AND HUMAN 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE-2 mRNA
DOI: http://dx.doi.org/10.30970/sbi.0402.141
Abstract
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is a key regulatory enzyme of glucose metabolism. This bifunctional enzyme controls glycolysis and gluconeogenesis as well as glucose phosphorylation and metabolism. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2 (PFKFB-2) plays significant role in the glycolysis regulation in the heart as well as in some other organs (kidney, brain and lung). Results of this investigation clearly demonstrated that in the glioma cells as well as in some mouse organs are presented several new unique alternative splice variants of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2. These PFKFB-2 splice variants are a result of deletions or/and inserts in catalytic regions of 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase as well as in С-terminal regulatory region. Alternative splice variants of PFKFB-2 from glioma and mouse cells contain different inserts after 2nd exon but mouse splice variant has also deletion in 6-phosphofructo-2-kinase region and insert in C-terminus. Another splice variants of mouse PFKFB-2 have deletions in 6-phosphofructo-2-kinase or fructose-2,6-bisphosphatase regions, since one splice variant has deletion of all catalytic domains. In conclusion, this study provides evidences that alternative splicing of PFKFB-2 mRNA possibly has a significant role in glycolysis regulation via creation of monofunctional isoforms of this enzyme.
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1. Okar D. A., Lange A. J. Fructose-2,6-bisphosphate and control of carbohydrate metabolism in eukaryotes. Biofactors, 1999; 10 (1): 1-14. | |
| |
2. Wu C., Khan S.A., Peng L.-J., Lange A. J. Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: beyond its allosteric effects on glycolytic and gluconeogenic enzymes. Edvans Enzyme Regulation, 2006; 46: 72-82. | |
| |
3. Okar D.A., Manzano A., Navarro-Sabate A. et al. PFK-2/FBPase 2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochemical Sciences, 2001; 26 (1): 30-35. | |
| |
4. Rider M. H., Bertrand L., Vertommen D. et al. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase: head-head with a bifunctional enzyme that controls glycolysis. Biochemical Journal, 2004; 381(Pt. 3): 561-579. | |
| |
5. Мінченко Д.О., Бобарикіна А.Ю., Кундієва А.В. та ін. Структурна організація, експресія та регуляція експресії генів 6-фосфофрукто-2-кінази/фруктозо-2,6-бісфосфатази. Біологічні студії/Studia Biologica, 2009; 3(3): 123-140. | |
| |
6. Bensaad K., Tsuruta A., Selak M.A. et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell, 2006; 126: 107-120. | |
| |
7. Clem B., Telang S., Clem A. et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Molecular Cancer Therapy, 2008; 7(1): 110-120. | |
| |
8. Calvo M. N., Bartrons R., Castaño E. et al. PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independence growth in HeLa cells. FEBS Letters, 2006; 580 (13): 3308-3314. | |
| |
9. Atsumi T., Nishio T., Niwa H. et al. Expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase/PFKFB3 isoforms in adipocytes and their potential role in glycolytic regulation. Diabetes, 2005; 54(12): 3349-3357. | |
| |
10. Minchenko A. G., Leshchinsky I., Opentanova I. L. et al. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. The Journal of Biological Chemistry, 2002; 277(8): 6183-6187. | |
| |
11. Minchenko O., Opentanova I., Caro J. Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Letters, 2003; 554(3): 264-270. | |
| |
12. Marsin A.-S., Douzin C., Bertrand L., Hue L. The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. The Journal of Biological Chemistry, 2002; 277 (40): 30778-30783. | |
| |
13. Atsumi T., Chesney J., Metz C. et al. High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (iPFK-2; PFKFB3) in human cancers. Cancer Research, 2002; 62(20): 5881-5887. | |
| |
14. Minchenko O. H., Opentanova I. L., Minchenko D. O. et al. Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 gene via hypoxia-inducible factor-1alpha activation. FEBS Letters, 2004; 576(1): 14-20. | |
| |
15. 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. Molecular and Cellular Biochemistry, 2005; 280(1-2): 227-234. | |
| |
16. Bobarykina A.Y., Minchenko D.O., Opentanova I.L. et al. Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers. Acta Biochimica Polonica, 2006; 53 (4): 789-799. | |
| |
17. Heine-Suner D., Diaz-Guillen M.A., Lange A.J., Rodriguez de Cordoba S. Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2). European Journal Biochemistry, 1998; 254 (1): 103-110. | |
| |
18. Marsin A., Bertrand L., Rider M. H., Deprez J. Phosphorylation and activation of heart PFK-2 by AMPK has role in the stimulation of glycolysis during ischemia. Currant Biology, 2000; 10: 1247-1255. | |
| |
19. Hue L., Beauloye C., Bertrand L. et al. New targets of AMP-activated kinase. Biochemical Society Transactions, 2003; 31 (1): 213-215. | |
| |
20. Donti R., Ye G., Wu C., Lange A. J. Cardiac expression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase inhibits glycolysis, promotes hypertrophy, impairs myocyte function and reduces insulin sensitivity. The Journal of Biological Chemistry, 2004; 279 (46): 48085-48090. | |
| |
21. Мінченко Д.О., Ковтун О.О., Мінченко О.Г., Биць Ю.В. Родина альтернативних сплайс-варіантів мРНК 6-фосфофрукто-2-кінази/фруктозо-2,6-бісфосфатази-4. Науковий вісник Національного медичного університету ім. О.О. Богомольця, 2006; 4: 72-78. | |
| |
22. Minchenko D.O., Tsuchihara K., Komisarenko S.V. et al. Unique alternative splice variants of mouse PFKFB-3 mRNA: tissue specific expression. Scientific Bulletin National O.O. Bohomoletz Medical University, 2008; N 1: 22-31. | |
| |
23. Watanabe F., Furuya E. Alternative splicing of novel exons rat heart type fructose-6-phosphate-2-kinase/fructose-2,6-bisphosphatase gene. Biochemical Biophysical Research Communications, 2001; 282: 803-810. | |
| |
24. Липова Н.М., Мінченко Д.О., Ратушна О.О. та ін. Експресія мРНК 6-фосфофрукто-2-кінази/фруктозо-2,6-бісфосфатази-2 та її альтернативних сплайс-варіантів у щурів з експериментальним цукровим діабетом. Український біохімічний журнал, 2010; 82(1): 90-99. | |
| |
25. Dedieu S., Canron X., Rezvani H.R. et al. The cytoprotective drug amifostine modifies both expression and activity of the pro-angiogenic factor VEGF-A. BMC Medicine, 2010; 8: 19. |
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