High impact information on ERG2

• Overexpression of the sterol isomerase-encoding gene, ERG2, confers enhanced SR resistance [1].
• We found that the cdc50Delta mutation is synthetically lethal with mutations affecting the late steps of ergosterol synthesis (erg2 to erg6) [2].
• We isolated a mutant defective in the internalization step of endocytosis in a gene (ERG2) encoding a C-8 sterol isomerase that acts in the late part of the ergosterol biosynthetic pathway [3].
• In the absence of Erg2p, yeast cells accumulate sterols structurally different from ergosterol, which is the major sterol in wild-type yeast [3].
• Interestingly, the deduced amino acid sequence was found to be related to fungal C8-C7 sterol isomerase, encoded by the ERG2 gene [4].

Biological context of ERG2

• Importantly, the purified DNA binding domain of Upc2p bound in vitro to putative sterol response elements in the ERG2 promoter, suggesting that Upc2p increases the expression of the ERG genes by directly binding to their promoters [5].
• In addition, a 2 mu plasmid overexpression of the ERG2 sequence did not produce FpR [6].
• When grown under azole drug pressure, the parental, heterozygous deletion and reconstructed strains of CaUPC2 upregulate the ERG2 and ERG11 ergosterol biosynthesis genes, while the homozygous deletion strain shows no such upregulation [7].
• We demonstrate that erg2 and erg24 mutants are viable in the deletion consortium background but are lethal when combined in the same haploid strain [8].
• 9E10 c-myc antibodies specifically immunoprecipitated the c-myc tagged protein after [3H]haloperidol photolabeling, unequivocally proving that the drug binding site is localized on the ERG2 gene product [9].

Anatomical context of ERG2

• Indeed the sigma ligands [3H]haloperidol (Kd = 0.3 nM) and [3H]ifenprodil (Kd = 1.4 nM) bound to a single population of sites in ERG2 wild type yeast microsomes (Bmax values of 77 and 61 pmol/mg of protein, respectively), whereas binding activity was absent in strains carrying ERG2 gene mutations or disruptions [9].

Associations of ERG2 with chemical compounds

• These profiles were compared to the transcript profiles of strains containing deletions of one of the late-stage ergosterol genes: ERG2, ERG5, or ERG6 [10].
• ERG2 and ERG24 are yeast sterol biosynthetic genes which are targets of morpholine antifungal compounds [8].
• The ERG2 gene product has been identified recently as the molecular target of SR 31747A that mediates antiproliferative effects of the drug in yeast [4].
• Exogenously-supplied zymosterol is entirely transformed into ergosterol, which represses ERG2 transcription [11].
• Together with an absence of gene dosage effect for ERG2 on fenpropimorph sensitivity, this supports the hypothesis that sterol delta 8-->7-isomerase inhibition does not contribute to the fungicidal activity of fenpropimorph [12].

Other interactions of ERG2

• A mutation in an otherwise nonessential ERG2 gene is synthetically lethal when combined with mutations in two transcription factors encoded by the UPC2 and ECM22 genes [13].
• In order to determine whether the ERG2 gene was essential for yeast viability, a LEU2 gene was inserted into the NdeI site (made blunt) of this 1.0 kb fragment [14].
• Erg2p and Erg3p, two enzymes catalyzing sequential reactions also appear to have different interaction partners [15].

References