TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
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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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TIGAR (C12orf5) functions in glycolysis by degrading fructose-2,6-bisphosphate, and thereby opposing the Warburg effect.
“The TP53-induced glycolysis and apoptosis regulator, encoded by p53 target gene TIGAR (C12orf5), functions in glycolysis by degrading fructose-2,6-bisphosphate, and thereby opposing the Warburg effect.37”
From Census and evaluation of p53 target genes (2017) · cites this paper as [37]
p53 regulates transcription of TIGAR and SCO2, which have key roles in glucose utilization and mitochondrial respiration.
“This link has been strengthened by recent reports that p53 regulates the transcription of two proteins, TP53-induced glycolosis and apoptosis regulator (TIGAR) and the SCO cytochrome oxidase deficient homologue 2 (SCO2), which have key roles in the utilization of glucose and mitochondrial respiration, respectively 83, 84 .”
From The common biology of cancer and ageing (2007) · cites this paper as [83]
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- Authors
- Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Corresponding author
- Vousden, Karen H.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 126
- Issue
- 1
- Pages
- 107-120
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2119239003
- Cited by
- 2,019
- References
- 44
- Citations by year
- 2026: 72 · 2025: 79 · 2024: 89 · 2023: 96 · 2022: 106 · 2021: 125 · 2020: 99 · 2019: 120 · 2018: 105 · 2017: 97 · 2016: 112 · 2015: 114 · 2014: 144 · 2013: 152 · 2012: 129
- FWCI
- 32.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2573 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Cancer Research UK
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- TIGAR, p53, glycolysis, apoptosis, fructose-2,6-bisphosphate, reactive oxygen species, tumor suppressor, cell death, genome stability
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Survival, Cell Transformation, Neoplastic, Chromosomes, Human, Pair 12, DNA Damage, DNA Repair, Energy Metabolism, Fructosediphosphates, Gene Expression Regulation, Glycolysis, Fructose-Bisphosphatase, Humans, Molecular Sequence Data, Phosphoric Monoester Hydrolases, Proteins, Signal Transduction, Down-Regulation, Tumor Suppressor Protein p53, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Genomic Instability, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins
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