Difference between revisions of "Phosphatase Subfamily TIGAR"
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| − | TIGAR | + | TIGAR stands for TP53 Induced Glycolysis Regulatory phosphatase. It inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and autophagy activity. It actually inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy <cite>Xie14</cite>. |
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| + | TIGAR can function as fructose- 2,6-bisphosphatase (Fru-2,6-BPase) <cite>bensaad06, li09</cite>, the same function with PFKFB1 of [[Phosphatase_Subfamily_PFKFB|PFKFB]]. (PS: functional redundancy?) Through promotion of the pentose phosphate pathway, it increases NADPH production to help limit reactive oxygen species (ROS). | ||
Under hypoxia, a fraction of TIGAR protein relocalized to mitochondria and formed a complex with hexokinase 2 (HK2), resulting in an increase in HK2 activity. The ability of TIGAR to function as a Fru-2,6-BPase was independent of HK2 binding and mitochondrial localization, although both of these activities can contribute to the full activity of TIGAR in limiting mitochondrial ROS levels and protecting from cell death <cite>cheung12</cite>. | Under hypoxia, a fraction of TIGAR protein relocalized to mitochondria and formed a complex with hexokinase 2 (HK2), resulting in an increase in HK2 activity. The ability of TIGAR to function as a Fru-2,6-BPase was independent of HK2 binding and mitochondrial localization, although both of these activities can contribute to the full activity of TIGAR in limiting mitochondrial ROS levels and protecting from cell death <cite>cheung12</cite>. | ||
Revision as of 17:35, 2 June 2015
Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily TIGAR
Vertebrate TIGAR functions as a fructose- 2,6-bisphosphatase, which results in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. TIGAR is also found in some basal eumetazoan, but is absent from nematodes and arthropoda.
Evolution
TIGAR is found in chordates and some basal eumetazoan, but is absent from nematodes and arthropoda.
Domain
TIGAR has a single domain: HP1 phosphatase.
Functions
TIGAR stands for TP53 Induced Glycolysis Regulatory phosphatase. It inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and autophagy activity. It actually inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy [1].
TIGAR can function as fructose- 2,6-bisphosphatase (Fru-2,6-BPase) [2, 3], the same function with PFKFB1 of PFKFB. (PS: functional redundancy?) Through promotion of the pentose phosphate pathway, it increases NADPH production to help limit reactive oxygen species (ROS).
Under hypoxia, a fraction of TIGAR protein relocalized to mitochondria and formed a complex with hexokinase 2 (HK2), resulting in an increase in HK2 activity. The ability of TIGAR to function as a Fru-2,6-BPase was independent of HK2 binding and mitochondrial localization, although both of these activities can contribute to the full activity of TIGAR in limiting mitochondrial ROS levels and protecting from cell death [4].
References
- Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, and Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006 Jul 14;126(1):107-20. DOI:10.1016/j.cell.2006.05.036 |
- Li H and Jogl G. Structural and biochemical studies of TIGAR (TP53-induced glycolysis and apoptosis regulator). J Biol Chem. 2009 Jan 16;284(3):1748-54. DOI:10.1074/jbc.M807821200 |
- Cheung EC, Ludwig RL, and Vousden KH. Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20491-6. DOI:10.1073/pnas.1206530109 |
