Disease relevance of FAS1

• Molecular structure of the multifunctional fatty acid synthetase gene of Brevibacterium ammoniagenes: its sequence of catalytic domains is formally consistent with a head-to-tail fusion of the two yeast genes FAS1 and FAS2 [1].

High impact information on FAS1

• Balanced levels of subunits alpha and beta are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits [2].
• In Saccharomyces cerevisiae, FAS1, FAS2, and FAS3 are the genes involved in saturated fatty acid biosynthesis [3].
• Deletion analyses of the regulatory regions of FAS1 and FAS2 revealed common regulatory sequences [3].
• 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 [4].
• Complementation of mutations and nucleotide sequence of FAS1 gene encoding beta subunit of yeast fatty acid synthase [5].

Biological context of FAS1

• In contrast, FAS1 expression becomes Ino2p-independent in nmt1-451D cells at temperatures where efficient acylation of cellular N-myristoylproteins is jeopardized [6].
• In addition, we show by random-breakage mapping that TRP3 is located approximately 45 kb from the left telomere of chromosome XI, whereas FAS1 is approximately 110 kb from the same telomere [7].
• Surprisingly, the first 66 nt of the FAS2 coding region turned out as necessary and sufficient for FAS1-dependent gene expression [8].
• FAS2-lacZ fusion constructs deleted for this region showed high reporter gene expression even in the absence of FAS1, arguing for a negatively-acting downstream repression site (DRS) responsible for FAS1-dependent expression of FAS2 [8].
• When a FAS2 multicopy plasmid is present in the cells, expression of both FAS1 and FAS3 increases [3].

Anatomical context of FAS1

• The ability to maintain expression of FAS1 in nmt1-451Dino2 Delta cells suggests the existence of another transcription factor, or factors, whose expression/activity is inversely related to overall levels of cellular protein N-myristoy-lation [6].

Associations of FAS1 with chemical compounds

• These changes are associated with a net increase in expression of some inositol target genes, including FAS1 . FAS1 encodes one of the subunits of the fatty acid synthase complex that catalyzes de novo acylCoA (including myristoylCoA) biosynthesis [6].
• Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline [2].
• The fatty acid synthetase (FAS) gene FAS1 of the alkane-utilizing yeast Yarrowia lipolytica was cloned and sequenced [9].

Other interactions of FAS1

• Compared to the intact alpha 6 beta 6 complex, the individual FAS subunits synthesized in the delta fas1 or delta fas2 strains exhibit a considerably increased sensitivity towards the proteinases present in the yeast cell homogenate [10].
• We have investigated the influence of a functional INO4 gene previously described as a regulator of inositol biosynthesis on the expression of FAS1 and FAS2 [11].
• Finally, we mapped the GPM1 gene 13 cM distal to fas1 on chromosome XI [12].

Analytical, diagnostic and therapeutic context of FAS1

• Molecular cloning of the yeast fatty acid synthetase genes, FAS1 and FAS2: illustrating the structure of the FAS1 cluster gene by transcript mapping and transformation studies [13].
• Southern blot analysis of C. albicans chromosomes separated by pulsed-field gel electrophoresis showed that FAS1 resides on chromosome 5 [14].
• However, site-directed mutagenesis of the respective cis-acting elements upstream of FAS1 and FAS2 revealed that additional sequences activating both genes must exist [15].

References