TIGAR Protein, Human (TAT)

TIGAR (TP53-induced glycolysis and apoptosis regulator) functions as a fructose-bisphosphatase, hydrolyzing fructose-2,6-bisphosphate and fructose-1,6-bisphosphate. Operating as a negative regulator of glycolysis, TIGAR reduces intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, thereby activating the pentose phosphate pathway (PPP) and promoting NADPH production. This regulatory activity contributes to the cellular defense against oxidative or metabolic stress-induced cell death by decreasing reactive oxygen species (ROS) content. TIGAR's role extends to protecting cells during hypoxia, where it lowers mitochondria ROS levels independently of its fructose-bisphosphatase activity through a mechanism involving hexokinase 2 (HK2). In contexts such as cardiac damage stress, TIGAR mediates p53-induced inhibition of myocyte mitophagy, influencing ROS levels and exacerbating apoptotic myocyte cell death. Additionally, TIGAR plays vital roles in adult intestinal regeneration, neuroprotection against ischemic brain damage, and promoting cancer cell survival by enhancing DNA repair through PPP activation in response to hypoxia and/or genome stress-induced DNA damage.