TIGAR Gene: Function, Expression, and Role in Cancer Metabolism

TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) is a p53-inducible gene that encodes a protein with fructose-2,6-bisphosphatase activity. It functions to lower intracellular fructose-2,6-bisphosphate levels, thereby inhibiting glycolysis and directing glucose flux into the pentose phosphate pathway. This promotes NADPH production and glutathione regeneration, protecting cells from reactive oxygen species (ROS)-induced apoptosis. TIGAR is implicated in cancer metabolism, where its expression can confer a survival advantage to tumor cells under metabolic stress.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycolysis / Gluconeogenesis (Reactome: R-HSA-70171)

• Pentose phosphate pathway (Reactome: R-HSA-71336)

• p53-dependent G1 DNA damage response (Reactome: R-HSA-69541)

• Regulation of glycolysis by fructose 2

• 6-bisphosphate (Reactome: R-HSA-9634600)

The TIGAR protein is a 270-amino acid enzyme that shares structural similarity with the bisphosphatase domain of PFKFB family members. It catalyzes the hydrolysis of fructose-2,6-bisphosphate to fructose-6-phosphate and inorganic phosphate, thereby lowering the allosteric activator of phosphofructokinase-1 (PFK1). This reduces glycolytic flux and diverts glucose-6-phosphate into the pentose phosphate pathway, increasing NADPH and glutathione levels. The protein is predominantly cytosolic and is induced by p53 in response to stress signals, contributing to cell survival by limiting ROS accumulation.