TP53-induced glycolysis and apoptosis regulator (TIGAR) (TIGAR)

TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53-inducible enzyme that plays a pivotal role in coordinating cellular metabolism and antioxidant responses (UniProt Q9NQ88). It functions as a fructose-2,6-bisphosphatase, which lowers the levels of fructose-2,6-bisphosphate, thereby inhibiting glycolysis and redirecting glucose-6-phosphate into the pentose phosphate pathway (PPP) (Bensaad et al., 2006, PMID: 16439209). This metabolic redirection increases the production of NADPH and reduced glutathione, which are essential for scavenging reactive oxygen species (ROS) and protecting cells from oxidative damage (Lee et al., 2014, PMID: 24711453). In the context of oncology, TIGAR is frequently overexpressed in various tumors, where it promotes cell survival and resistance to apoptosis induced by chemotherapy or radiation (Tang et al., 2021, PMID: 33854974). Consequently, TIGAR is considered a promising therapeutic target, with strategies focusing on the use of antisense oligonucleotides or siRNA to degrade TIGAR mRNA and sensitize cancer cells to oxidative stress (Wanka et al., 2012, PMID: 22825330). Beyond cancer, TIGAR's role in modulating ROS has implications in ischemia-reperfusion injury and neurodegenerative diseases, where its regulation may offer cytoprotective benefits (Zhou et al., 2016, PMID: 27050158). Current research is actively exploring small molecule inhibitors and RNA-based therapies to modulate TIGAR activity for clinical applications.

Other names

C12orf5Fructose-2,6-bisphosphatase TIGARTP53-induced glycolysis and apoptosis regulator

Degradation of TIGAR mRNA via RNA interference or antisense mechanisms to deplete the TIGAR protein, leading to increased glycolytic flux, reduced antioxidant capacity, and elevated reactive oxygen species (ROS) levels.