Glyoxalase II, a detoxifying enzyme of glycolysis byproduct methylglyoxal and a target of p63 and p73, is a pro-survival factor of the p53 family

Yang Xu, Xinbin Chen

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The p53 family proteins are transcription factors and have both common and distinct functions. p53 is a classic tumor suppressor, whereas p63 and p73 have fundamental functions in development. To gain an insight into the functional diversities among the p53 family, target genes specifically regulated by p63 and p73 were examined. Here, we found that the GLX2 gene, which encodes glyoxalase II enzyme, is up-regulated by p63 and p73. Accordingly, a specific responsive element was found in intron 1 of the GLX2 gene, which can be activated and bound by p63 and p73. We also found that, upon overexpression, the cytosolic, but not the mitochondrial, GLX2 inhibits the apoptotic response of a cell to methylglyoxal, a by-product of glycolysis. Likewise, we showed that cells deficient in GLX2 are hypersensitive to methylglyoxal-induced apoptosis. Interestingly, a deficiency in GLX2 also enhances the susceptibility of a cell to DNA damage-induced apoptosis in a p53-dependent manner. These observations reveal a novel link between the p53 family and the glyoxalase system. Given that methylglyoxal is frequently generated under both physiological and pathological conditions, we postulate that GLX2 serves as a pro-survival factor of the p53 family and plays a critical role in the normal development and in the pathogenesis of various human diseases, including cancer, diabetes, and neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)26702-26713
Number of pages12
JournalJournal of Biological Chemistry
Volume281
Issue number36
DOIs
StatePublished - Sep 8 2006
Externally publishedYes

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hydroxyacylglutathione hydrolase
Pyruvaldehyde
Glycolysis
Byproducts
Genes
Survival
Enzymes
Neurodegenerative diseases
Apoptosis
Medical problems
Neurodegenerative Diseases
Introns
DNA Damage
Tumors
Neoplasms
Transcription Factors
DNA
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "Glyoxalase II, a detoxifying enzyme of glycolysis byproduct methylglyoxal and a target of p63 and p73, is a pro-survival factor of the p53 family",
abstract = "The p53 family proteins are transcription factors and have both common and distinct functions. p53 is a classic tumor suppressor, whereas p63 and p73 have fundamental functions in development. To gain an insight into the functional diversities among the p53 family, target genes specifically regulated by p63 and p73 were examined. Here, we found that the GLX2 gene, which encodes glyoxalase II enzyme, is up-regulated by p63 and p73. Accordingly, a specific responsive element was found in intron 1 of the GLX2 gene, which can be activated and bound by p63 and p73. We also found that, upon overexpression, the cytosolic, but not the mitochondrial, GLX2 inhibits the apoptotic response of a cell to methylglyoxal, a by-product of glycolysis. Likewise, we showed that cells deficient in GLX2 are hypersensitive to methylglyoxal-induced apoptosis. Interestingly, a deficiency in GLX2 also enhances the susceptibility of a cell to DNA damage-induced apoptosis in a p53-dependent manner. These observations reveal a novel link between the p53 family and the glyoxalase system. Given that methylglyoxal is frequently generated under both physiological and pathological conditions, we postulate that GLX2 serves as a pro-survival factor of the p53 family and plays a critical role in the normal development and in the pathogenesis of various human diseases, including cancer, diabetes, and neurodegenerative diseases.",
author = "Yang Xu and Xinbin Chen",
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