TIGAR, a p53-inducible regulator of glycolysis and apoptosis.
The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
Bensaad
Karim
K
The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK.
Tsuruta
Atsushi
A
Selak
Mary A
MA
Vidal
M Nieves Calvo
MN
Nakano
Katsunori
K
Bartrons
Ramon
R
Gottlieb
Eyal
E
Vousden
Karen H
KH
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics; D006597:Fructose-Bisphosphatase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D042822:Genomic Instability / Q000502:physiology; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D005635:Fructosediphosphates; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D006597:Fructose-Bisphosphatase; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human; C029063:fructose-1,6-diphosphate