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Cytological research

TIGAR: A Novel p53-Inducible Gene Regulating Glycolysis

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— 1 min read

Scientists at Brown University have made a significant discovery in the field of cancer research by identifying a novel p53-inducible gene, TIGAR, which plays a crucial role in regulating glycolysis. TIGAR, short for TP53-induced glycolysis and apoptosis regulator, inhibits glycolysis by reducing cellular levels of fructose-2,6-bisphosphate. The researchers conducted structural and biochemical studies on TIGAR from Danio rerio and found that it forms a histidine phosphatase fold with a phosphate molecule coordinated to the catalytic histidine residue.

Key Takeaways:

  • TIGAR is a novel p53-inducible gene that inhibits glycolysis by reducing cellular levels of fructose-2,6-bisphosphate.
  • The researchers conducted structural and biochemical studies on TIGAR from Danio rerio and found that it forms a histidine phosphatase fold with a phosphate molecule coordinated to the catalytic histidine residue.
  • The TIGAR active site is open and positively charged, consistent with its enzymatic function as bisphosphatase.
  • The closest related structures to TIGAR are the bacterial broad specificity phosphatase PhoE and the fructose-2,6-bisphosphatase domain of the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
  • The structural comparison shows that TIGAR combines an accessible active site with a charged substrate-binding pocket.
  • TIGAR hydrolyzes fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate but not fructose 6-phosphate in vitro.
  • The researchers concluded that TIGAR's enzymatic function as bisphosphatase is essential for its role in regulating glycolysis.
  • The study provides new insights into the mechanisms of cancer cell metabolism and potential therapeutic targets.

Statistics:

  • The study was published in the Journal of Biological Chemistry in 2009.
  • The research was conducted by scientists at Brown University, with H. Li and colleagues as the primary authors.
  • The study focused on TIGAR from Danio rerio and its enzymatic function as bisphosphatase.
  • The researchers analyzed the structural and biochemical properties of TIGAR and found that it forms a histidine phosphatase fold.
  • TIGAR's active site is open and positively charged, consistent with its enzymatic function.
  • The closest related structures to TIGAR are the bacterial broad specificity phosphatase PhoE and the fructose-2,6-bisphosphatase domain of the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Sources:

  • Li, H., et al. "Structural and Biochemical Studies of TIGAR (TP53-induced Glycolysis and Apoptosis Regulator)." Journal of Biological Chemistry, vol. 284, no. 3, 2009, pp. 1748-1754.
  • Journal of Biological Chemistry.
  • Brown University.

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