TY - JOUR
T1 - TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
AU - Bensaad, Karim
AU - Tsuruta, Atsushi
AU - Selak, Mary A.
AU - Vidal, M. Nieves Calvo
AU - Nakano, Katsunori
AU - Bartrons, Ramon
AU - Gottlieb, Eyal
AU - Vousden, Karen H.
N1 - Funding Information:
We would like to thank Jane Steel for antibody production and Billy Clark for sequencing. We are extremely grateful to Robert Ludwig for his help with EMSA and expression analyses. This work was funded by Cancer Research UK and the Ministerio de Educación y Ciencia (BMC 2003/01442), Spain.
PY - 2006/7/14
Y1 - 2006/7/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2006.05.036
DO - 10.1016/j.cell.2006.05.036
M3 - Article
C2 - 16839880
AN - SCOPUS:33745918951
SN - 0092-8674
VL - 126
SP - 107
EP - 120
JO - Cell
JF - Cell
IS - 1
ER -