PFKFB4 explained

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 also known as PFKFB4 is an enzyme which in humans is encoded by the PFKFB4 gene.^{[1] [2]}

Function

The bifunctional 6-phosphofructo-2-kinase /fructose-2,6-bisphosphatase (PFKFB) regulates the steady-state concentration of fructose 2,6-bisphosphate, an activator of a key regulatory enzyme of glycolysis, phosphofructokinase.

In 2012 research by scientists at Cancer Research UK’s London Research Institute show that an enzyme called PFKFB4 is essential for balancing these two processes – making sure the cell’s energy needs are met without allowing free radicals to build up and trigger cell death.Study leader Dr. Almut Schulze, said: “Our study suggests that PFKFB4 acts to fine-tune the process by which cells convert glucose into energy. Blocking this enzyme in prostate cancer cells grown in the lab stalled growth and triggered a catastrophic build-up of free-radicals, suggesting that it could be a suitable drug target. Importantly, this route to energy production is common to many different types of cancer, suggesting that drugs to target it could potentially be used to treat a variety of cancers.”^[3]

Further reading

• Pilkis SJ, Claus TH, Kurland IJ, Lange AJ . 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme . Annual Review of Biochemistry . 64 . 1 . 799–835 . 1995 . 7574501 . 10.1146/annurev.bi.64.070195.004055 .
• Gómez M, Manzano A, Navarro-Sabaté A, Duran J, Obach M, Perales JC, Bartrons R . Specific expression of pfkfb4 gene in spermatogonia germ cells and analysis of its 5'-flanking region . FEBS Letters . 579 . 2 . 357–62 . January 2005 . 15642344 . 10.1016/j.febslet.2004.11.096 . 33170865 .
• Minchenko OH, Ochiai A, Opentanova IL, Ogura T, Minchenko DO, Caro J, Komisarenko SV, Esumi H . Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors . Biochimie . 87 . 11 . 1005–10 . November 2005 . 15925437 . 10.1016/j.biochi.2005.04.007 .
• Minchenko O, Opentanova I, Minchenko D, Ogura T, Esumi H . Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation . FEBS Letters . 576 . 1–2 . 14–20 . October 2004 . 15474002 . 10.1016/j.febslet.2004.08.053 . 20380862 . free .
• Bobarykina AY, Minchenko DO, Opentanova IL, Moenner M, Caro J, Esumi H, Minchenko OH . 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 . 53 . 4 . 789–99 . 2006 . 17143338 . 10.18388/abp.2006_3308. free .
• Ros S, Santos CR, Moco S, Baenke F, Kelly G, Howell M, Zamboni N, Schulze A . Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 as an important regulator of prostate cancer cell survival . Cancer Discovery . 2 . 4 . 328–43 . 2012 . 22576210 . 10.1158/2159-8290.CD-11-0234 . free .

Notes and References

1. Sakai A, Kato M, Fukasawa M, Ishiguro M, Furuya E, Sakakibara R . Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human placenta . Journal of Biochemistry . 119 . 3 . 506–11 . March 1996 . 8830046 . 10.1093/oxfordjournals.jbchem.a021270 .
2. Manzano A, Pérez JX, Nadal M, Estivill X, Lange A, Bartrons R . Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene . Gene . 229 . 1–2 . 83–9 . March 1999 . 10095107 . 10.1016/S0378-1119(99)00037-2 .
3. Ros S, Santos CR, Moco S, Baenke F, Kelly G, Howell M, Zamboni N, Schulze A . Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 as an important regulator of prostate cancer cell survival . Cancer Discovery . 2 . 4 . 328–43 . April 2012 . 22576210 . 10.1158/2159-8290.CD-11-0234 . free .