Disease relevance of DPL1

• Cells unable to break down long-chain-base phosphates, due to deletion of DPL1 and LCB3, show a 500-fold increase in PHS-1-P and DHS-1-P levels, grow slowly, and survive a 44 degreesC heat stress 10-fold better than parental cells [1].

High impact information on DPL1

• To identify genes involved in LCBP signaling and in regulation of LCBP synthesis, we performed transposon mutagenesis in cells lacking the LCBP lyase DPL1 and LCBP phosphatase LCB3 genes and screened for phytosphingosine-resistant clones [2].
• Deletion of the mitochondrial PE pathway gene PSD1 was synthetically lethal with the crd1delta mutant, whereas deletion of the Golgi and endoplasmic reticulum pathway genes PSD2 and DPL1 did not result in synthetic lethality [3].
• Overexpression of GATA-4 led to both an increase in activity of a reporter gene as well as an increase in endogenous sphingosine-1-phosphate lyase protein [4].
• Sphingosine-1-phosphate is irreversibly degraded by the highly conserved enzyme sphingosine-1-phosphate lyase [4].
• In this study, regulation of sphingosine-1-phosphate lyase gene expression was investigated in Caenorhabditis elegans, where lyase expression is spatially restricted to cells of the developing and adult gut and is essential for normal development [4].

Biological context of DPL1

• The phenotypes of the ysr2 sur2 mutants were suppressed by overexpression of DPL1 [5].
• Chromosomal localization mapped this SPL gene to Chromosome 10 at 32 cM [6].
• Using the C. elegans SPL nucleotide sequence, we identified a mouse EST as a putative candidate for the homologous gene encoding this enzyme [6].

Anatomical context of DPL1

• Because DPL1 also partially suppresses the growth and secretion phenotypes of a snc deletion, we propose that enhanced degradation of dihydrosphingosine-1-phosphate allows an alternative protein to replace Sncp as the secretory vesicle v-SNARE [7].

Associations of DPL1 with chemical compounds

• Mutants lacking both S1P lyase and phosphatase (dpl1 lcb3 double mutants) exhibited constitutively high Ca(2+) accumulation and signaling in the absence of added sphingosine, and these effects were dependent on the sphingosine kinases [8].
• DPL1, the structural gene for dihydrosphingosine phosphate lyase, was selected as a high copy number snc1-M43A suppressor [7].
• These studies implicate a role for DPL1 and phosphorylated sphingoid bases in the regulation of global responses to nutrient deprivation in yeast [9].

References