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Gene Review

ARE2  -  Are2p

Saccharomyces cerevisiae S288c

Synonyms: N3206, SAT1, Sterol O-acyltransferase 2, Sterol-ester synthase 2, YNR019W
 
 
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Disease relevance of ARE2

  • Our results indicate that transcriptional regulation of ARE genes by heme and specific substrate preferences of Are1p and Are2p may be involved in the adaptation of yeast sterol metabolism to hypoxia [1].
 

High impact information on ARE2

  • Deletion of ARE2 reduced sterol ester levels to approximately 25 percent of normal levels, whereas disruption of ARE1 did not affect sterol ester biosynthesis [2].
  • In vitro microsomal assays verified that DGA1 and ARE2 mediate acyl-CoA:diacylglycerol acyltransferase reactions [3].
  • However, diploids that are homozygous for a SAT1 null mutation exhibit significantly reduced sporulation efficiency [4].
  • A serine-to-leucine mutation in the (H/Y)SF motif (residues 338-340), unique to sterol esterification enzymes, nullified the activity and stability of yeast Are2p [5].
  • Similarly, a tyrosine-to-alanine change in the FYxDWWN motif of Are2p (residues 523-529) produced an enzyme with decreased activity and apparent affinity for oleoyl-CoA [5].
 

Biological context of ARE2

 

Anatomical context of ARE2

 

Associations of ARE2 with chemical compounds

  • We present evidence that the primary role of the minor sterol esterification isoform encoded by ARE1 is to esterify sterol intermediates, whereas the role of the ARE2 enzyme is to esterify ergosterol, the end product of the pathway [6].
  • ARE2 overexpression had no impact on the accumulation of the early sterols such as lanosterol, but influenced the later intermediates and the end product ergosterol [9].
  • Steryl esters are formed by the two steryl ester synthases Are1p and Are2p, two enzymes with overlapping function which also catalyze triacylglycerol formation, although to a minor extent [10].
 

Other interactions of ARE2

  • In a growth competition experiment are1are2 cells grow more slowly than wild-type after several rounds of cultivation, suggesting that Are1p and Are2p or steryl esters, the product formed by these two enzymes, are more important in the natural environment than under laboratory conditions [11].
  • In addition to recovering multiple alleles of previously identified genes required for this process (referred to as alpha 2 repression), we have identified four other genes, designated ARE1, ARE2, ARE3, and ARE4 (for alpha 2 repression) [12].

References

  1. Heme-regulated expression of two yeast acyl-CoA:sterol acyltransferases is involved in the specific response of sterol esterification to anaerobiosis. Valachovic, M., Klobucníková, V., Griac, P., Hapala, I. FEMS Microbiol. Lett. (2002) [Pubmed]
  2. Sterol esterification in yeast: a two-gene process. Yang, H., Bard, M., Bruner, D.A., Gleeson, A., Deckelbaum, R.J., Aljinovic, G., Pohl, T.M., Rothstein, R., Sturley, S.L. Science (1996) [Pubmed]
  3. The DGA1 gene determines a second triglyceride synthetic pathway in yeast. Oelkers, P., Cromley, D., Padamsee, M., Billheimer, J.T., Sturley, S.L. J. Biol. Chem. (2002) [Pubmed]
  4. Molecular cloning and characterization of two isoforms of Saccharomyces cerevisiae acyl-CoA:sterol acyltransferase. Yu, C., Kennedy, N.J., Chang, C.C., Rothblatt, J.A. J. Biol. Chem. (1996) [Pubmed]
  5. Identification of potential substrate-binding sites in yeast and human acyl-CoA sterol acyltransferases by mutagenesis of conserved sequences. Guo, Z., Cromley, D., Billheimer, J.T., Sturley, S.L. J. Lipid Res. (2001) [Pubmed]
  6. Transcriptional regulation of the two sterol esterification genes in the yeast Saccharomyces cerevisiae. Jensen-Pergakes, K., Guo, Z., Giattina, M., Sturley, S.L., Bard, M. J. Bacteriol. (2001) [Pubmed]
  7. An acyl-CoA:cholesterol acyltransferase (ACAT)-related gene is involved in the accumulation of triacylglycerols in Saccharomyces cerevisiae. Sandager, L., Dahlqvist, A., Banaś, A., Ståhl, U., Lenman, M., Gustavsson, M., Stymne, S. Biochem. Soc. Trans. (2000) [Pubmed]
  8. A yeast strain lacking lipid particles bears a defect in ergosterol formation. Sorger, D., Athenstaedt, K., Hrastnik, C., Daum, G. J. Biol. Chem. (2004) [Pubmed]
  9. Enhanced sterol-acyl transferase activity promotes sterol accumulation in Saccharomyces cerevisiae. Polakowski, T., Bastl, R., Stahl, U., Lang, C. Appl. Microbiol. Biotechnol. (1999) [Pubmed]
  10. Dynamics of neutral lipid storage in yeast. Müllner, H., Daum, G. Acta Biochim. Pol. (2004) [Pubmed]
  11. Contribution of Are1p and Are2p to steryl ester synthesis in the yeast Saccharomyces cerevisiae. Zweytick, D., Leitner, E., Kohlwein, S.D., Yu, C., Rothblatt, J., Daum, G. Eur. J. Biochem. (2000) [Pubmed]
  12. Identification of genes required for alpha 2 repression in Saccharomyces cerevisiae. Wahi, M., Johnson, A.D. Genetics (1995) [Pubmed]
 
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