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Gene Review

CYB2  -  Cyb2p

Saccharomyces cerevisiae S288c

Synonyms: Cytochrome b2, mitochondrial, L-LCR, L-lactate ferricytochrome C oxidoreductase, YM9958.08C, YML054C
 
 
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High impact information on CYB2

  • The internal deletion of the seven repeated amino acid sequences containing the KCPVDH motif in the CYP1(HAP1) protein modifies the heme responsiveness phenomenon observed in vitro in the band-shift experiments and in vivo in the transcription of the CYB2, CYC1, CYP3(CYC7) and ERG11 genes [1].
  • The yeast CYB2 gene encodes an L-lactate:cytochrome c oxidoreductase that oxidizes lactate, donates electrons directly into the mitochondrial respiratory chain, and supports lactate-dependent respiration [2].
  • Furthermore, we have shown that the CYB2 promoter contains one cis negative regulatory region and two heme-dependent positive regions, one of which is controlled by the transcriptional regulator CYP1 (HAP1) which is involved in the modulation of the expression of several oxygen-regulated genes [3].
  • These studies indicated that regulation of the CYB2 gene is subject to several metabolic controls at the transcriptional level: inhibition due to glucose fermentation, induction by lactate, and inhibition in anaerobiosis or in absence of heme biosynthesis [3].
  • In this study, we show that Hap1p is the main transcriptional activator involved in the control of CYB2 transcription [4].
 

Biological context of CYB2

  • Selection for mutants which release glucose repression of the CYB2 gene was used to identify genes which regulate repression of mitochondrial biogenesis [5].
  • We found that Hap1p activity, known to be oxygen dependent, is effected by DNA-protein interaction with two binding sites present in the CYB2 promoter [4].
  • Transformation of the mutant with a K. lactis genomic library allowed the isolation of the KlCYB2 gene, restoring the growth on lactate and the L-LCR activity [6].
 

Associations of CYB2 with chemical compounds

  • The DLD gene was cloned by complementation for growth on D-, L-lactate in the strain WWF18-3D, carrying both a CYB2 disruption and the dld mutation [7].
  • These results are discussed together with the role of L-LCR and D-LCR in lactate metabolism of S. cerevisiae [7].
  • We selected several lactate- pyruvate+ mutants in a cyb2 genetic background [7].
 

Other interactions of CYB2

  • Finally, our results suggest that the Adr1p transcriptional activator is also required in CYB2 transcription control [4].

References

  1. Evidence for an interaction between the CYP1(HAP1) activator and a cellular factor during heme-dependent transcriptional regulation in the yeast Saccharomyces cerevisiae. Fytlovich, S., Gervais, M., Agrimonti, C., Guiard, B. EMBO J. (1993) [Pubmed]
  2. Introduction of an additional pathway for lactate oxidation in the treatment of lactic acidosis and mitochondrial dysfunction in Caenorhabditis elegans. Grad, L.I., Sayles, L.C., Lemire, B.D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Complex transcriptional regulation of the Saccharomyces cerevisiae CYB2 gene encoding cytochrome b2: CYP1(HAP1) activator binds to the CYB2 upstream activation site UAS1-B2. Lodi, T., Guiard, B. Mol. Cell. Biol. (1991) [Pubmed]
  4. Regulation of the CYB2 gene expression: transcriptional co-ordination by the Hap1p, Hap2/3/4/5p and Adr1p transcription factors. Ramil, E., Agrimonti, C., Shechter, E., Gervais, M., Guiard, B. Mol. Microbiol. (2000) [Pubmed]
  5. Regulation of nuclear genes encoding mitochondrial proteins in Saccharomyces cerevisiae. Brown, T.A., Evangelista, C., Trumpower, B.L. J. Bacteriol. (1995) [Pubmed]
  6. Cloning and characterization of the lactate-specific inducible gene KlCYB2, encoding the cytochrome b(2) of Kluyveromyces lactis. Alberti, A., Goffrini, P., Ferrero, I., Lodi, T. Yeast (2000) [Pubmed]
  7. Isolation of the DLD gene of Saccharomyces cerevisiae encoding the mitochondrial enzyme D-lactate ferricytochrome c oxidoreductase. Lodi, T., Ferrero, I. Mol. Gen. Genet. (1993) [Pubmed]
 
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