Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Saccharomyces cerevisiae, FAS1, FAS2, and FAS3 are the genes involved in saturated fatty acid biosynthesis. The enzymatic activities of both fatty acid synthase (FAS) and acetyl-CoA carboxylase are reduced 2- to 3-fold when yeast cells are grown in the presence of exogenous fatty acids. The mRNA levels of the FAS genes are correspondingly lower under repressive conditions. Expression of the FAS-lacZ reporter gene is also regulated by fatty acids. When a FAS2 multicopy plasmid is present in the cells, expression of both FAS1 and FAS3 increases. Thus, the FAS genes are coordinately regulated. Deletion analyses of the regulatory regions of FAS1 and FAS2 revealed common regulatory sequences. These include the GGCCAAAAAC and AGCCAAGCA sequences that have a common GCCAA core sequence and the UASINO (upstream activation sequence). Derepression of the FAS genes in the absence of exogenous inositol is not observed when UASINO is mutated, indicating that this cis element is a positive regulator of these genes. The GCCAA elements and UASINO act synergistically for optimal expression of the FAS genes.
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PMID:Coordinated regulation and inositol-mediated and fatty acid-mediated repression of fatty acid synthase genes in Saccharomyces cerevisiae. 135 36

Mutations in the Saccharomyces cerevisiae SNF1 gene affect a number of cellular processes, including the expression of genes involved in carbon source utilization and phospholipid biosynthesis. To identify targets of the Snf1 kinase that modulate expression of INO1, a gene required for an early, rate-limiting step in phospholipid biosynthesis, we performed a genetic selection for suppressors of the inositol auxotrophy of snf1Delta strains. We identified mutations in ACC1 and FAS1, two genes important for fatty acid biosynthesis in yeast; ACC1 encodes acetyl coenzyme A carboxylase (Acc1), and FAS1 encodes the beta subunit of fatty acid synthase. Acc1 was shown previously to be phosphorylated and inactivated by Snf1. Here we show that snf1Delta strains with increased Acc1 activity exhibit decreased INO1 transcription. Strains carrying the ACC1 suppressor mutation have reduced Acc1 activity in vitro and in vivo, as revealed by enzymatic assays and increased sensitivity to the Acc1-specific inhibitor soraphen A. Moreover, a reduction in Acc1 activity, caused by addition of soraphen A, provision of exogenous fatty acid, or conditional expression of ACC1, suppresses the inositol auxotrophy of snf1Delta strains. Together, these findings indicate that the inositol auxotrophy of snf1Delta strains arises in part from elevated Acc1 activity and that a reduction in this activity restores INO1 expression in these strains. These results reveal a Snf1-dependent connection between fatty acid production and phospholipid biosynthesis, identify Acc1 as a Snf1 target important for INO1 transcription, and suggest models in which metabolites that are generated or utilized during fatty acid biosynthesis can significantly influence gene expression in yeast.
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PMID:Inhibition of acetyl coenzyme A carboxylase activity restores expression of the INO1 gene in a snf1 mutant strain of Saccharomyces cerevisiae. 1148 11