Difference between revisions of "Phosphatase Subfamily TIGAR"

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_TIGAR|Subfamily TIGAR]]
 
[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_TIGAR|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.
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TIGAR inhibits glycolysis and negatively modulates the level of intracellular reactive oxygen species (ROS), therefore regulating autophagy and apoptosis. TIGAR is found in chordates some basal [[Phosphatase_Glossary#Eumetazoa|eumetazoan]], but is absent from nematodes and arthropoda.
  
 
=== Evolution ===
 
=== Evolution ===

Revision as of 18:20, 2 June 2015

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily TIGAR

TIGAR inhibits glycolysis and negatively modulates the level of intracellular reactive oxygen species (ROS), therefore regulating autophagy and apoptosis. TIGAR is found in chordates 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 domain.

Functions

TIGAR stands for TP53 Induced Glycolysis and Apoptosis Regulatory phosphatase [1]. It inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and therefore autophagic response [1, 2]. It also inhibits apoptosis [3]. It is not surprising that TIGAR is implicated in cancer, such as intestinal cancer [4].

TIGAR inhibits glycolysis by functioning as fructose- 2,6-bisphosphatase (Fru-2,6-BPase) [1, 5] and/or 23BPG (2,3-bisphosphoglycerate) [6]. It is worthy pointing out that PFK2 (phosphofructokinase 2) of PFKFB subfamily functions as Fru-2,6-BPase, and the reported catalytic efficiency of TIGAR as an Fru-2,6-BPase is several orders of magnitude lower than that of PFK2.

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 [7].

References

  1. 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 | PubMed ID:16839880 | HubMed [bensaad06]
  2. Bensaad K, Cheung EC, and Vousden KH. Modulation of intracellular ROS levels by TIGAR controls autophagy. EMBO J. 2009 Oct 7;28(19):3015-26. DOI:10.1038/emboj.2009.242 | PubMed ID:19713938 | HubMed [Bensaad09]
  3. Xie JM, Li B, Yu HP, Gao QG, Li W, Wu HR, and Qin ZH. TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer Res. 2014 Sep 15;74(18):5127-38. DOI:10.1158/0008-5472.CAN-13-3517 | PubMed ID:25085248 | HubMed [Xie14]
  4. 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 | PubMed ID:19015259 | HubMed [li09]
  5. Gerin I, Noël G, Bolsée J, Haumont O, Van Schaftingen E, and Bommer GT. Identification of TP53-induced glycolysis and apoptosis regulator (TIGAR) as the phosphoglycolate-independent 2,3-bisphosphoglycerate phosphatase. Biochem J. 2014 Mar 15;458(3):439-48. DOI:10.1042/BJ20130841 | PubMed ID:24423178 | HubMed [Gerin14]
  6. 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 | PubMed ID:23185017 | HubMed [cheung12]
  7. Cheung EC, Athineos D, Lee P, Ridgway RA, Lambie W, Nixon C, Strathdee D, Blyth K, Sansom OJ, and Vousden KH. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev Cell. 2013 Jun 10;25(5):463-77. DOI:10.1016/j.devcel.2013.05.001 | PubMed ID:23726973 | HubMed [Cheung12]
All Medline abstracts: PubMed | HubMed