Activity of the Yap1 transcription factor in Saccharomyces cerevisiae is modulated by methylglyoxal, a metabolite derived from glycolysis

Molecular and Cellular Biology
Kazuhiro MaetaYoshiharu Inoue

Abstract

Methylglyoxal (MG) is synthesized during glycolysis, although it inhibits cell growth in all types of organisms. Hence, it has long been asked why such a toxic metabolite is synthesized in vivo. Glyoxalase I is a major enzyme detoxifying MG. Here we show that the Yap1 transcription factor, which is critical for the oxidative-stress response in Saccharomyces cerevisiae, is constitutively concentrated in the nucleus and activates the expression of its target genes in a glyoxalase I-deficient mutant. Yap1 contains six cysteine residues in two cysteine-rich domains (CRDs), i.e., three cysteine residues clustering near the N terminus (n-CRD) and the remaining three cysteine residues near the C terminus (c-CRD). We reveal that any of the three cysteine residues in the c-CRD is sufficient for MG to allow Yap1 to translocate into the nucleus and to activate the expression of its target gene. A Yap1 mutant possessing only one cysteine residue in the c-CRD but no cysteine in the n-CRD and deletion of the basic leucine zipper domain can concentrate in the nucleus with MG treatment. However, substitution of all the cysteine residues in Yap1 abolishes the ability of this transcription factor to concentrate in the nucleus following MG treatm...Continue Reading

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Citations

Jan 16, 2010·Applied Microbiology and Biotechnology·Wataru NomuraYoshiharu Inoue
Nov 24, 2006·Applied and Environmental Microbiology·Kazuhiro MaetaYoshiharu Inoue
Apr 28, 2009·Eukaryotic Cell·Sadri ZnaidiMartine Raymond
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Mar 19, 2014·TheScientificWorldJournal·Halyna M Semchyshyn
Nov 19, 2008·Biochemical and Biophysical Research Communications·Yusuke NakadateTaro Tachibana
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Oct 9, 2012·Environmental Microbiology·Lina BarretoJoaquín Ariño
Nov 8, 2014·IUBMB Life·Sangeeta ChakrabortyDipshikha Chakravortty
Nov 18, 2005·Biochemical and Biophysical Research Communications·Lijo JohnBeena Pillai
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Feb 4, 2010·The Biochemical Journal·Yoshifumi TakatsumeYoshiharu Inoue
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Aug 12, 2020·Journal of Experimental & Clinical Cancer Research : CR·Stefano MeniniGiuseppe Pugliese
Nov 7, 2018·Applied Microbiology and Biotechnology·Joana T CunhaLucília Domingues

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