Disease relevance of TPS1

• In contrast, membrane traffic operated many hours after severe heat stress even in the absence of the TPS1 gene, demonstrating that trehalose had no role in thermoprotection of membranes engaged in vesicular traffic [1].
• Analysis of the otsBA operon for osmoregulatory trehalose synthesis in Escherichia coli and homology of the OtsA and OtsB proteins to the yeast trehalose-6-phosphate synthase/phosphatase complex [2].
• Upon induction of tps1, trehalose increased, and this was associated with increased tolerance to anoxia [3].

High impact information on TPS1

• Upon return to 30 degrees C, TPS1, TPS2, and HSP104 mRNAs, trehalose levels and tolerance to freezing fall dramatically within minutes [4].
• This is illustrated by a detailed kinetic analysis of a paradoxical Saccharomyces cerevisiae mutant; the mutant fails to grow on glucose because of overactive initial enzymes of glycolysis, but is defective only in an enzyme (trehalose 6-phosphate synthase) that appears to have little relevance to glycolysis [5].
• Mutants deficient in both glucose-induced signalling and the control of initial glucose metabolism have a defect in the trehalose-6-phosphate synthase catalytic subunit of the trehalose synthase complex [6].
• Deletion of FPS1 does not cause any of the phenotypic deficiencies of the fdp1 mutant [7].
• The deficiency of the fdp1 mutant in glucose-induced RAS-mediated cAMP signalling and in rapid glucose-induced changes in the activity of certain enzymes was not restored [7].

Chemical compound and disease context of TPS1

• However, they also indicate that the yeast TPS enzyme, as opposed to the E. coli otsA gene product, is able to increase the efficiency of the Tre6P control on glucose influx into yeast glycolysis [8].
• Complementation studies with E. coli galU mutants showed that the TPS1-encoded trehalose-6-phosphate synthase is UDP-glucose-dependent [9].

Biological context of TPS1

• Thus we suggest that Gts1p plays a major role in the oscillatory expression of TPS1 and SUC2 in continuous cultures of Saccharomyces cerevisiae, and hypothesized that Gts1p stabilizes oscillations in energy metabolism by activating trehalose synthesis to facilitate glycolysis at the shift from the respiratory to the respiro-fermentative phase [10].
• The amino acid sequence encoded by ZrTPS1 has relatively high homology with TPS1 of Saccharomyces cerevisiae and Schizosaccharomyces pombe, compared with TPS2 [11].
• The mRNA levels of genes for Hsp104 and trehalose-6-phosphate synthase 1 changed as a function of GTS1 gene dosage [12].
• Treatment with 0.6 M sorbitol induced small but reproducible differences, with gene expression higher in the CIF1 strain compared to the cif1 mutant [13].
• Evidence that the Saccharomyces cerevisiae CIF1 (GGS1/TPS1) gene modulates heat shock response positively [14].

Anatomical context of TPS1

• In permeabilized spheroplasts, hexokinase activity is significantly lower in a tps2Delta strain compared to a wild-type strain and this difference is strongly reduced by additional deletion of TPS1 [15].

Associations of TPS1 with chemical compounds

• Among the four genes studied, TPS1 is necessary and sufficient for growth on glucose and fructose [16].
• Deletion of TPS1 results in severe hyperaccumulation of sugar phosphates and near absence of ethanol formation [15].
• Enhanced glycerol production caused by overexpression of GPD1 encoding glycerol-3-phosphate dehydrogenase also suppressed the growth defect of ggs1/tps1 delta mutants, suggesting a novel role for glycerol production in the control of glycolysis [17].
• The same effect was seen in the tps1 (trehalose-6-phosphate synthase) hsp104 double mutant, suggesting that the extreme heat shock sensitivity was due mainly to a lack of trehalose rather than to the presence of trehalose-6-phosphate [18].
• When cultures were exposed to 0.8 M NaCl or 1.5 M sorbitol the cif1 strain showed greatly reduced transcription of osmotically induced genes compared to the wild type [13].

Physical interactions of TPS1

• When the temperature of exponential-phase cultures of Saccharomyces cerevisiae was abruptly raised from 28 to 40 degrees C, trehalose immediately accumulated, whereas the activities of trehalase and trehalose-6-phosphate synthase/trehalose-6-phosphate phosphatase complex increased after a lag period of about 10 min [19].

Regulatory relationships of TPS1

• Afterwards, the Tps1-dependent control system is apparently able to restrict properly up to 50-fold higher hexokinase activity [20].
• Furthermore, high-copy MCK1 or heterozygous hxk2 mutations can suppress the tps1 sporulation trait [21].
• It was observed that the PKC1 pathway was hardly activated in a tps1 mutant that is unable to accumulate any trehalose [22].

Other interactions of TPS1

• Since we observed measurable trehalose in strains lacking all but the TPS1 gene, some phosphatase activity in addition to Tps2 can hydrolyze trehalose 6-phosphate [16].
• Our results show that overexpression of hexokinase does not cause the same phenotype as deletion of Tps1 [20].
• During the initiation of fermentation overexpression of hexokinase PII in yeast transiently causes a similar deregulation of glycolysis as deletion of Tps1 [20].
• The expression of genes repressed by cAMP, GAC1 and TPS1, fused to beta-galactosidase, was also stimulated by deletion of SSA genes [23].
• These genes are located on chromosomes II (TSS1) and XIII (TSL1) [24].

Analytical, diagnostic and therapeutic context of TPS1

• Western blot analysis showed that the antibody against S. cerevisiae TPS1 recognizes ZrTPS1 [11].
• Molecular cloning of CIF1, a yeast gene necessary for growth on glucose [25].
• Complementation tests showed that cif1 is not allelic to fdp1 although the two genes seem to be functionally related [25].
• This activation was accompanied by a decrease of some 20 kDa in the molecular mass of a cluster of SDS-PAGE bands at about 115 kDa recognized by antiserum to pure TPS/P, but by no change in the 57 kDa band [26].
• Both isogenic strains inherited a partially reverted cif1 phenotype, designated CPR, from the trehalose-deficient progenitor that had been used in construction of the non-isogenic strains [27].

References