Disease relevance of PPX1

• The PPX1 gene encoding the major cytosolic exopolyPase does not encode the nuclear one and its inactivation has no effect on polyP metabolism in this compartment [1].
• With regard to the first subject, it has been shown that E. coli cells in which yeast exopolyphosphatase (poly(P)ase), PPX1, was overproduced reduced resistance to H2O2 and heat shock as did a mutant whose polyphosphate kinase gene is disrupted [2].

High impact information on PPX1

• To explore the role of poly P in mammalian cells, a yeast polyphosphatase, PPX1, was inserted into the chromosomes of MCF-7 mammary cancer cells [3].
• A double mutant of PPN1 and PPX1 (the gene encoding a potent exopolyphosphatase) loses viability rapidly in stationary phase [4].
• Yeast exopolyphosphatase (scPPX) processively splits off the terminal phosphate group from linear polyphosphates longer than pyrophosphate. scPPX belongs to the DHH phosphoesterase superfamily and is evolutionarily close to the well characterized family II pyrophosphatase (PPase) [5].
• An exopolyphosphatase (polyphosphate phosphohydrolase; EC 3.6.1.11) activity that cleaves inorganic polyphosphates to orthophosphate has been purified to apparent homogeneity (> 95% pure) from Saccharomyces cerevisiae [6].
• In the absence of these ions, the exopolyphosphatase binds to polyphosphate but does not degrade it, allowing affinity purification of the enzyme on a polyphosphate-modified zirconia support. o-Vanadate, Cu2+, and Ca2+ are effective inhibitors of the exopolyphosphatase [6].

Chemical compound and disease context of PPX1

• The exopolyPase activity was nearly the same with polyphosphate (polyP) chain lengths ranging from 3 to 208 orthophosphate when measured with Mg2+ [7].
• The high-molecular-mass exopolyphosphatase hydrolyzes polyP with an average chain length of 208 to 15 phosphate residues to the same extent, but is inactive with ATP, PPi, and p-nitrophenyl phosphate [8].

Biological context of PPX1

• The gene encoding a major exopolyphosphatase (scPPX1) in Saccharomyces cerevisiae (H. Wurst and A. Kornberg, J. Biol. Chem. 269:10996-11001, 1994) has been isolated from a genomic library [9].
• Therefore, the membrane-bound exopolyphosphatase of mitochondria and the high-molecular-mass enzyme of the cytosol of S. cerevisiae are not encoded by the PPX1 gene, unlike the soluble low-molecular-mass exopolyphosphatase of mitochondria, which is probably a product of this gene with a posttranslational modification [10].
• Hydrolysis of tripolyphosphate by purified exopolyphosphatase from Saccharomyces cerevisiae cytosol: kinetic model [11].
• The kinetics of hydrolysis of tripolyphosphate by purified exopolyphosphatase from Saccharomyces cerevisiae cytosol has been studied in the presence of Mg2+ [11].

Anatomical context of PPX1

• Inactivation of the PPX1 gene encoding exopolyphosphatase had no effect on respiration functions and on polyphosphate level and chain length in mitochondria [12].
• The PPX1 gene responsible for 40-kD exopolyphosphatase of the cytosol does not encode it [8].
• Disruption of PPX1 in strains with and without deficiencies in vacuolar proteases allowed the identification of exopolyphosphatase activity in the vacuole [9].

Associations of PPX1 with chemical compounds

• Unlike the enzyme encoded by PPX1, the high-molecular-mass exopolyphosphatase is slightly active with polyP3, not inhibited by antibodies suppressing the activity of 40-kD exopolyphosphatase, inhibited by EDTA, and stimulated by divalent cations to a lesser extent [8].
• RNA does not alter the nuclear exopolyphosphatase activity, while polylysine increases it 2-fold [13].
• Cycloheximide blocks the increase in activity of high molecular weight exopolyphosphatase and hence, under these conditions the latter is synthesized de novo [14].
• The expression of the high molecular weight exopolyphosphatase is due to the acceleration of metabolism in cells that have reached the stage of growth deceleration on the addition of P(i) and glucose or complete culture medium [15].

References