Disease relevance of SPE1

• This cDNA was functionally expressed in strains of Escherichia coli and Saccharomyces cerevisiae that lack ODC and are dependent upon exogenous PA for survival [1].
• Expression of MTAP in MTAP-deleted MCF-7 breast adenocarcinoma cells results in a significant reduction of ODC activity and reduction in polyamine levels [2].

High impact information on SPE1

• Induction of neuronal differentiation and ornithine decarboxylase (ODCase) transcription by oncogenic p21N-ras does not occur in compactin-treated cells indicating that activity of oncogenic p21N-ras expressed in PC12 cells is abolished by compactin treatment [3].
• As the cell density increases, there is a marked fall in the level of ornithine decarboxylase (ODC) in the MEU1(+) cells, which we show is caused by an antizyme-requiring degradation system [4].
• [Subhi, A. L., et al. (2003) J. Biol. Chem. 278, 49868-49873] of a novel regulatory pathway in meu1Delta cells in which ODC is not responsive to spermidine [4].
• The meu1Delta cells have a higher putrescine and a lower spermidine level than MEU1(+) cells, suggesting that the decreased spermidine level in the meu1Delta cultures is responsible for the greater apparent stability of ODC in the meu1Delta cells [4].
• Molecular dynamics simulations have been used to derive the structures of ground (orotidine-5'-monophosphate decarboxylase x orotidine 5'-monophosphate; ODC x OMP) and intermediate (ODC x intermediate; ODC x I(-)) states in the ODC-catalyzed decarboxylation of OMP [5].

Chemical compound and disease context of SPE1

• ABA-spermine is a potent inhibitor of ornithine decarboxylase from Escherichia coli, giving 50% inhibition at 0.12 mM, while ANB-spermine is a modest inhibitor, comparable to spermine or spermidine [6].

Biological context of SPE1

• The high level of +1 ribosomal frameshifting efficiency in spe2 delta cells is the result of the combined effects of both spermidine deprivation and the large increase in the level of intracellular putrescine resulting from the derepression of the gene for ornithine decarboxylase (SPE1) in spermidine-deficient strains [7].
• SPE1 and SPE2: two essential genes in the biosynthesis of polyamines that modulate +1 ribosomal frameshifting in Saccharomyces cerevisiae [7].
• Four transformants, three of which contain plasmids with the SPE1 gene, were isolated by selection on polyamine-free medium [8].
• We isolated several strains of Saccharomyces cerevisiae containing mutations mapping at a single chromosomal gene (spe10); these strains are defective in the decarboxylation of L-ornithine to form putrescine and consequently do not synthesize spermidine and spermine [9].
• The gene for ornithine decarboxylase in Saccharomyces cerevisiae, SPE1, has been assigned to chromosome XI by the technique of transverse alternating pulsed field electrophoresis and DNA-DNA hybridization [10].

Anatomical context of SPE1

• We have found that in S. cerevisiae, as in other eukaryotic cells, the rate of degradation of ornithine decarboxylase, measured either enzymatically or immunologically, is increased by the addition of spermidine to a yeast culture [11].
• The amount of ODC mRNA and the number of ribosomes associated with the mRNA were constant despite the variations in ODC activity [12].
• Here, we show that yeast and mouse ODC are both rapidly degraded in yeast cells and that their degradation severely inhibited in a mutant yeast cell line defective in the chymotryptic activity of proteinase yscE, the yeast 20S proteasome [13].
• The addition of the penultimate salvage pathway compound 4-methylthio-2-oxobutanoic acid represses ODC levels in both MTAP-deleted yeast and human tumor cell lines, indicating that 4-methylthio-2-oxobutanoic acid acts as a negative regulator of polyamine biosynthesis [2].
• Inhibition of the dimorphic transition of Candida albicans by the ornithine decarboxylase inhibitor 1,4-diaminobutanone: alterations in the glycoprotein composition of the cell wall [14].

Associations of SPE1 with chemical compounds

• The effect of added spermidine in the overexpressed SPE1 strains is best seen in spe2 mutants in which the initial intracellular spermidine is very low or absent [11].
• We have purified ornithine decarboxylase to homogeneity and shown that loss of ornithine decarboxylase activity resulting from growth with added spermidine and spermine is the result of post-translational modification [15].
• Experiments with cycloheximide show that new protein synthesis is required to effect the breakdown of the ornithine decarboxylase [11].
• Ornithine decarboxylase has been purified 1,500-fold to homogeneity from a spe2 mutant of Saccharomyces cerevisiae which lacks S-adenosylmethionine decarboxylase and is derepressed for ornithine decarboxylase [16].
• The ornithine decarboxylase is a single polypeptide (Mr = 68,000) and requires a thiol and pyridoxal phosphate for activity [16].

Other interactions of SPE1

• Since spe1 delta SPE2 cells can synthesize decarboxylated adenosylmethionine (dcAdoMet), these data indicate that dcAdoMet may be toxic to amine-deficient cells [17].
• This suggests that ornithine decarboxylase activity is negatively controlled by the presence of spermidine aminopropyltransferase [9].
• In both MEU1(+) and the meu1Delta cultures, the ODC levels were markedly decreased by the addition of spermidine to the media, and thus our results contradict the postulation of Subhi et al [4].
• Saccharomyces cerevisiae strains were obtained by one-step gene replacement of a 900 bp fragment of the yeast ODC gene (SPE1) with the yeast URA3 gene [18].
• However, the rest of the pathway including ornithine decarboxylase and spermidine synthase was probably inherited from bacterial genes present in the original host cell, common ancestor of plants and animals, that acquired the cyanobacterial endosymbiont [19].

Analytical, diagnostic and therapeutic context of SPE1

• The purified preparation from S. uvarum had an Mr of 73 000 and a 100-fold purification (purified by conventional methods) of ornithine decarboxylase from S. cerevisiae had an Mr of 69 000 on a gel filtration column [20].
• It appeared that S. uvarum ornithine decarboxylase could be highly purified by affinity chromatography, but S. cerevisiae enzyme did not bind to the same column [20].
• Southern blot analysis suggested that ornithine decarboxylase is a single-copy gene in S. cerevisiae [21].
• The ornithine decarboxylase gene from Candida albicans. Sequence analysis and expression during dimorphism [22].
• The gene (CaODC) coding for ornithine decarboxylase, a key enzyme in polyamine biosynthesis, was cloned from Candida albicans by PCR and characterized [22].

References