Disease relevance of DPP1

• Genes encoding for diacylglycerol pyrophosphate phosphatase have been isolated from S. cerevisiae and E. coli [1].

High impact information on DPP1

• Phosphatidate phosphatase (PAP) enzymes catalyze the dephosphorylation of phosphatidate, yielding diacylglycerol and inorganic phosphate [2].
• Roles of phosphatidate phosphatase enzymes in lipid metabolism [2].
• In eukaryotic cells, PAP activity has a central role in the synthesis of phospholipids and triacylglycerol through its product diacylglycerol, and it also generates and/or degrades lipid-signaling molecules that are related to phosphatidate [2].
• The Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate phosphatase is a vacuole membrane-associated enzyme that catalyzes the removal of the beta-phosphate from diacylglycerol pyrophosphate to form phosphatidate, and it then removes the phosphate from phosphatidate to form diacylglycerol [3].
• However, other enzyme activities, including phosphatidylinositol synthase and phosphatidate phosphatase, were not affected in the cki1Delta eki1Delta mutant [4].

Biological context of DPP1

• The expression of a membrane-associated form of phosphatidate phosphatase is regulated by growth phase and inositol supplementation, whereas enzyme activity is regulated by lipids, nucleotides, and by phosphorylation [1].
• Analysis of DPP1 expression using PDPP1-lacZ reporter genes with a series of deletions from the 5' end of the promoter indicated sequences responsible for enzyme expression [5].
• Disruption of either LPP1 or DPP1 caused respective decreases of about 25 and 75% in Mg2+-independent hydrolysis of several isoprenoid phosphates by particulate fractions isolated from these cells [6].
• Multicopy plasmids containing the DPP1 gene directed a 10-fold overexpression of DGPP phosphatase activity in S. cerevisiae [7].
• Three binding sites (URSPDS) for transcription factor Gis1p were identified in the DPP1 promoter (consensus sequence of 5'-T(A/T)AGGGAT-3') [5].

Anatomical context of DPP1

• Studies with well characterized subcellular fractions and by indirect immunofluorescence microscopy revealed that the DGPP phosphatase enzyme was localized to the vacuolar membrane [8].
• DGPP phosphatase was purified 33,333-fold from Saccharomyces cerevisiae by a procedure that included Triton X-100 solubilization of microsomal membranes followed by chromatography with DE53, Affi-Gel Blue, hydroxylapatite, and Mono Q [9].
• Phosphatidate phosphatase from yeast mitochondria [10].

Associations of DPP1 with chemical compounds

• The DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase enzyme accounts for half of the Mg2+-independent phosphatidate (PA) phosphatase activity in Saccharomyces cerevisiae [11].
• The Dol-P-P phosphatase encoded by CWH8 is optimally active in the presence of 0.5% octyl glucoside and relatively unstable in Triton X-100, distinguishing this activity from the lipid phosphatases encoded by LPP1 and DPP1 [12].
• This enzyme possesses a phosphatidate phosphatase activity which is Mg2+-independent and N-ethylmaleimide-insensitive and is distinct from the Mg2+-dependent and N-ethylmaleimide-sensitive form of phosphatidate phosphatase [1].
• Phosphatidate phosphatase plays a major role in the synthesis of phospholipids and triacylglycerols in the yeast Saccharomyces cerevisiae [1].
• The Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate phosphatase catalyzes the dephosphorylation of diacylglycerol pyrophosphate to form phosphatidate and Pi [5].

Regulatory relationships of DPP1

• Under zinc-deplete conditions, the positive transcription factor Zap1p stimulates the expression of the DPP1 and PIS1 genes through the cis-acting element UAS(ZRE) [13].

Other interactions of DPP1

• The LPP1 gene product also exhibited lyso-PA phosphatase and DGPP phosphatase activities [11].
• This regulation was dependent on the UAS(ZRE) in the DPP1 promoter and was mediated by the Zap1p transcriptional activator [8].
• Repression of DPP1 expression is mediated by the transcription factor Gis1p, which binds to three post-diauxic shift elements in the promoter [14].
• Regulation of the DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase by inositol and growth phase. Inhibition of DGPP phosphatase activity by CDP-diacylglyceron and activation of phosphatidylserine synthase activity by DGPP [15].

Analytical, diagnostic and therapeutic context of DPP1

• Direct interaction between Gis1p and DPP1 promoter elements was demonstrated by electrophoretic mobility shift assays [5].

References