PFKFB3

PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3) is an enzyme with a significant role in glycolysis regulation in rapidly dividing cells, including in cancer and during development. It is present in a wide variety of tissues and is activated under hypoxic conditions.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
5675 AZ PFKFB3 26
Potent and selective PFKFB3 inhibitor
5742 AZ PFKFB3 67
Potent and selective PFKFB3 inhibitor
5048 YZ9
PFKFB3 inhibitor

Other

Cat No Product Name / Activity
5121 3PO
PFKFB3 inhibitor
5339 PFK 15
Selective PFKFB3 inhibitor

Related Targets

PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3) is an enzyme that plays a key role in the regulation of glycolysis in rapidly dividing cells, so is important in cancer metabolism and during development. PFKFB3 is present in a wide variety of tissues and is induced under hypoxic conditions. The enzyme is one of four PFKFB isozymes and differs from other family members in that it has a very high kinase:phosphatase activity ratio and is overexpressed in a range of cancer types. It is important in the maintenance of fructose-2,6-bisphosphate (F2,6BP) levels in cells, which is an activator of 6-phosphofructo-1-kinase, a rate-limiting enzyme in glycolysis. It has been shown that inhibition of PFKFB3 reduces intracellular F2,6BP levels and suppresses glucose uptake and glycolysis.

PFKFB3 is also a substrate for APC/C (anaphase-promoting complex/cyclosome)-Cdh1, a ubiquitin ligase that controls progression along the cell cycle from G1- to S-phase. The inactivation of APC/C -Cdh1 during mid-to-late G1 results in a rise in PFKFB3 levels and a transient increase in lactate generation. Therefore the presence of PFKFB3 at this particular stage of the cell cycle ensures the upregulation of glycolysis and the provision of sufficient nutrients for cell division.

In addition, F2,6BP activates certain cyclin dependent kinases; in particular, it promotes the Cdk-mediated phosphorylation of p27. p27 has an important role in cell cycle regulation, suppressing transition from G1- to S-phase and promoting apoptosis. Phosphorylation of p27, however, leads to its ubiquitination and proteasomal degradation. So increased F2,6BP levels associated with upregulation of PFKFB3, as seen in cancerous cells, are associated with cell proliferation and inhibition of apoptosis.

Literature for PFKFB3

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Kinases

Kinases Product Listing

A collection of over 400 products for kinase research, the listing includes inhibitors of:

  • Receptor Tyrosine Kinases
  • Protein Kinases A, C, D and G
  • PI-3 Kinase, Akt and mTOR
  • MAPK Signaling
  • Receptor Serine/Threonine Kinases
Cell Cycle & DNA Damage Repair

Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.

Programmed Cell Death

Programmed Cell Death Poster

There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.

PFKFB3 Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
PFKFB3 Human PFKFB3 NM_004566 Q16875
Mouse Pfkfb3 NM_001177753 A7UAK5
Rat Pfkfb3 NM_057135 NP_476476