Difference between revisions of "Phosphatase Subfamily TIGAR"
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TIGAR stands for TP53 Induced Glycolysis and Apoptosis Regulatory phosphatase <cite>bensaad06</cite>. It inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and therefore autophagic response <cite> bensaad06, Bensaad09 </cite>. It also inhibits apoptosis <cite>Xie14</cite>. It is not surprising that TIGAR is implicated in cancer, such as intestinal cancer <cite>Cheung13</cite>. | TIGAR stands for TP53 Induced Glycolysis and Apoptosis Regulatory phosphatase <cite>bensaad06</cite>. It inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and therefore autophagic response <cite> bensaad06, Bensaad09 </cite>. It also inhibits apoptosis <cite>Xie14</cite>. It is not surprising that TIGAR is implicated in cancer, such as intestinal cancer <cite>Cheung13</cite>. | ||
| − | TIGAR inhibits glycolysis by functioning as fructose- 2,6-bisphosphatase (Fru-2,6-BPase) <cite>bensaad06, li09</cite> and/or 23BPG (2,3-bisphosphoglycerate) <cite>Gerin14</cite>. It is worthy pointing out that PFK2 (phosphofructokinase 2) of [[Phosphatase_Subfamily_PFKFB|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. | + | TIGAR inhibits glycolysis by functioning as fructose- 2,6-bisphosphatase (Fru-2,6-BPase) <cite>bensaad06, li09</cite> and/or 23BPG (2,3-bisphosphoglycerate) <cite>Gerin14</cite>. It is worthy pointing out that Fru-2,6-BP and 23BPG are the substrates of other HP genes. PFK2 (phosphofructokinase 2) of [[Phosphatase_Subfamily_PFKFB|PFKFB]] subfamily, HP1 family 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. MINPP1 of [[Phosphatase_Family_HP2|HP2]] family dephosphorylates 23BPG <cite>cho08</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>. | 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 20:37, 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 Fru-2,6-BP and 23BPG are the substrates of other HP genes. PFK2 (phosphofructokinase 2) of PFKFB subfamily, HP1 family 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. MINPP1 of HP2 family dephosphorylates 23BPG [7].
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 [8].
References
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