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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
TIGAR, a p53-inducible regulator of glycolysis and apoptosis
Karim Bensaad1, Atsushi Tsuruta, Mary A Selak
1The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK.
Abstract:
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.
Insights
The tumor suppressor p53 regulates cell death via the TIGAR gene. TIGAR reduces reactive oxygen species (ROS) and glycolysis, protecting cells from p53-induced apoptosis and genomic damage.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Metabolism
Background:
- The p53 tumor-suppressor protein is crucial for preventing cancer.
- p53 functions through cell-cycle arrest, apoptosis, and maintaining genome stability.
Purpose of the Study:
- Identify novel p53-inducible genes.
- Investigate the role of TIGAR (TP53-induced glycolysis and apoptosis regulator) in p53-mediated cellular responses.
Main Methods:
- Analysis of p53-inducible gene expression.
- Measurement of fructose-2,6-bisphosphate and intracellular reactive oxygen species (ROS) levels.
- Assessment of cellular apoptosis and sensitivity to p53-induced death.
Main Results:
- Identified TIGAR as a p53-inducible gene.
- TIGAR expression decreased fructose-2,6-bisphosphate, inhibiting glycolysis and lowering intracellular ROS.
- TIGAR protected cells from ROS-associated apoptosis; TIGAR knockdown sensitized cells to p53-induced death.
Conclusions:
- TIGAR modulates the apoptotic response to p53, promoting cell survival under stress.
- Reduced intracellular ROS by TIGAR contributes to p53's role in preventing genomic damage.
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