Disease relevance of PFKFB1

• 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 [1].
• Moreover, desferrioxamine and cobalt chloride, which mimic the effect of hypoxia by chelating or substituting for iron, had a similar stimulatory effect on the expression of PFKFB mRNA [2].
• Recently, we have shown that PFKFB4 gene which encodes the testis isoenzyme of PFKFB is also expressed in the prostate and hepatoma cancer cell lines [2].

High impact information on PFKFB1

• The structure at 2.1 A resolution shows that the overall folding and functional dimerization are very similar to those of the liver (PFKFB1) and testis (PFKFB4) forms, as expected from sequence homology [3].
• Although none of these mutations affected the interaction of GCK with PFKFB1, we found that the R308W mutation caused protein instability and increased the strength of interaction with GCKR [4].
• Our findings demonstrate involvement of SREBP-1a in the transcriptional activation of PFKFB1, and we conclude that SREBP-1a may exert a key role mediating postprandial activation of PFKFB1 transcription [5].
• Transient transfection of HepG2 cells with deleted gene promoter constructs and electrophoretic mobility shift assays allowed us to identify a sterol regulatory element (SRE) to which SRE binding protein-1a (SREBP-1a) binds and transactivates PFKFB1 gene transcription [5].
• 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key modulator of glycolysis-gluconeogenesis [5].

Biological context of PFKFB1

• 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) is a bifunctional enzyme, which is responsible for maintaining the cellular level of fructose-2,6-bisphosphate, a powerful allosteric activator of glycolysis [6].
• To gain insight into the molecular mechanism behind hormonal and nutritional regulation of PFKFB expression, we have cloned and characterized the proximal promoter region of the liver isoform of PFKFB (PFKFB1) from gilthead sea bream (Sparus aurata) [5].

Anatomical context of PFKFB1

• A significant negative correlation of the activity of F6PK with age is observed in brain cortex and putamen [7].

Associations of PFKFB1 with chemical compounds

• Two protein systems, the extracellular soluble domain of the human growth hormone receptor (hGHbp) and the phosphatase domain of PFKFB1 (BPase), were used for the study on effects of DMSO on protein stability, protein aggregation, and binding of drug compounds [8].

Other interactions of PFKFB1

• PFKFB3 (iPFK2) is one of four tissue-specific PFKFB isozymes that have been identified to date [9].

Analytical, diagnostic and therapeutic context of PFKFB1

• The in vivo binding of SREBP-1a to the SRE box in the S. aurata PFKFB1 promoter was confirmed by chromatin immunoprecipitation assays [5].
• PFKFB1 (previously PFRX), which encodes the liver and muscle isozymes, was assigned to Xq22-q31 in the rat and to Xq27-q28 in the human by in situ hybridization using probes generated by the polymerase chain reaction [10].

References