Disease relevance of CHO1

• The primary translation product contains a region showing local sequence homology with yeast phosphatidylserine synthase (EC 2.7.8.8) and Escherichia coli 3-phosphatidyl-1'-glycerol-3'-phosphate synthase (EC 2.7.8.5), suggesting that these three enzymes are evolutionarily related [1].
• Cloning, sequencing, and expression in Escherichia coli of the Bacillus subtilis gene for phosphatidylserine synthase [2].

High impact information on CHO1

• However, cho1 yeast strains that are unable to synthesize PS do not phenocopy drs2 but instead transport proteins normally via the secretory pathway [3].
• The expression of the INO1 and CHO1 target genes was still responsive to inositol even though expression of the INO2 gene was unresponsive [4].
• The reduced phosphatidylserine synthase activity in the bcy1 mutant correlated with elevated levels of a phosphorylated form of the phosphatidylserine synthase Mr 23,000 subunit [5].
• The elevated phosphatidylserine synthase activity in the cyr1 mutant correlated with reduced levels of the phosphorylated form of the enzyme [5].
• Phospho amino acid analysis of labeled phosphatidylserine synthase showed that the enzyme was phosphorylated at a serine residue [5].

Biological context of CHO1

• A nine bp sequence was identified in the promoter region of the CHO1 gene that shares an eight out of nine bp match with a sequence (consensus 5' ATGTGAAAT 3') that is repeated a total of 23 times upstream from several coregulated phospholipid biosynthetic genes [6].
• An open reading frame of 828 base pairs was found in the CHO1 gene region of Saccharomyces cerevisiae by nucleotide sequencing analysis [7].
• When cho1 mutant cells were transformed with the 2.8-kb subclone on a single-copy plasmid, the 1.2-kb RNA and PSS activity levels were regulated in a wild-type fashion [8].
• Regulation of phospholipid synthesis in the yeast cki1Delta eki1Delta mutant defective in the Kennedy pathway. The Cho1-encoded phosphatidylserine synthase is regulated by mRNA stability [9].
• The DNA sequence on an integrative plasmid was shown to recombine into the CHO1 locus, confirming its genetic identity [10].

Anatomical context of CHO1

• Partial purification of phosphatidylserine synthase from microsomes of this transformed strain confirmed that the membrane-bound enzyme was overproduced 6- to 7-fold as compared with the wild-type strain [10].
• In Saccharomyces cerevisiae, the membrane-associated enzyme phosphatidylserine synthase (EC 2.7.8.8) is present in the mitochondria and the endoplasmic reticulum [11].
• Glycerolphosphate acyltransferase, phosphatidylinositol synthase, and phosphatidylserine synthase were exposed at the cytosolic surface of the outer mitochondrial membrane [12].
• Pigmentation of cho1 ade2 double mutants was obscured and vacuoles of cho1 mutants were considerably fragmented [13].
• However, most of the truncated PSS protein accumulated in the cytosol in an inactive form [14].

Associations of CHO1 with chemical compounds

• Reduction in the level of CDP-DAG synthase activity from 10-fold over wild type levels to 10% of wild type levels results in a 7-fold increase in PS synthase activity, which follows a similar change in the CHO1/PSS mRNA level [15].
• Finally, valproate, but not lithium, increases expression of phosphatidylcholine pathway genes CHO1 and OPI3 [16].
• The larger protein was concluded to be the primary product of the CHO1 gene, since its amino-terminal sequence was identical to that deduced from the nucleotide sequence of the above open reading frame, except for the terminal methionine residue [7].
• The increase in phospholipid synthesis correlated with increased activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase [9].
• The CHO1-disrupted mutant, when grown on choline, accumulated phosphatidylethanolamine to a significant level even after extensive dilution of the initial culture [17].
• The increased CHO1 mRNA stability in response to respiratory deficiency caused increases in CHO1 mRNA abundance, phosphatidylserine synthase protein and activity, and the synthesis of phosphatidylserine in vivo [18].

Other interactions of CHO1

• Another regulatory mutation, opi1, which causes the constitutive derepression of PSS and other phospholipid biosynthetic enzymes, caused the constitutive derepression of the 1.2-kb RNA [8].
• Cells bearing the ino2 or ino4 regulatory mutations, which exhibit constitutively repressed levels of a number of phospholipid biosynthetic enzymes, had constitutively repressed levels of 1.2-kb RNA and PSS activity [8].
• Surprisingly, expression of genes that are usually derepressed during inositol depletion, including INO1, CHO1 and INO2 (that contain inositol-responsive UASINO sequences) decreased several fold during the first hour, after which expression began to increase [19].
• A strain carrying the tightest of the three alleles was examined in detail and was found to express the set of co-regulated phospholipid structural genes (INO1, CHO1, CHO2 and OP13) constitutively [20].
• These changes can be attributed to an increase in PIS1-encoded PI synthase activity and a decrease in the activities of several CDP-diacylglycerol pathway enzymes including the CHO1-encoded PS (phosphatidylserine) synthase [21].

Analytical, diagnostic and therapeutic context of CHO1

• Under the growth conditions where a reduction of enzyme activity occurred, there was a corresponding qualitative reduction of enzyme subunit as determined by immunoblotting with antiserum raised against purified phosphatidylserine synthase [22].

References