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Literature summary for 3.1.1.116 extracted from

  • Walker, D.; Suetterlin, P.; Reisenberg, M.; Williams, G.; Doherty, P.
    Down-regulation of diacylglycerol lipase-alpha during neural stem cell differentiation identification of elements that regulate transcription (2010), J. Neurosci. Res., 88, 735-745 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
gene DAGLalpha, identification of the core promoter region and regulatory elements of DAGLalpha, specificity protein 1 (Sp1), is the only factor that can bind to the GC-box, the core promoter contains both an enhancer and a suppressor region. The GC-box specifically promotes expression in NS cells. Functional transient recombinant expression of pGL3-DAGLalpha promoter constructs plus pRLTK Renilla plasmid in NS cells. Promoter activity study of promoters P1-P11, overview. The full-length DAGLa promoter (P1) is active in Cor-1, CGR8, and NS-5 NS cell lines. A comparative analysis of the eight most relevant promoter constructs in the Cor-1 cells shows that P6 is the smallest and most active promoter. Again, the activity of P6 is suppressed by the 3' region, as revealed with P8, P10, and in this case also P11. The loss of DAGLa promoter luciferase activity in Cor-1 cells is due to a loss of function specific to the GC-box. The core DAGLa promoter is under a different regulatory control in the different cell types and identify two independent elements that can specifically regulate expression in Cor-1 cells. The GC-box is required for DAGLa core promoter activity in Cor-1 cells but not in 3T3 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information a dominant negative Sp1 is shown to bind to the GC-box and to suppress DAGLalpha promoter activity specifically in NS cells Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane
-
Homo sapiens 16020
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O Homo sapiens
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2-arachidonoylglycerol + fatty acid
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y4D2
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-
CGR-8 cell
-
Homo sapiens
-
Cor-1 cell
-
Homo sapiens
-
embryonic stem cell
-
Homo sapiens
-
additional information DAGLalpha protein is downregulated in Cor-1 cells during neuronal differentiation Homo sapiens
-
neural stem cell
-
Homo sapiens
-
NS-5 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O
-
Homo sapiens 2-arachidonoylglycerol + fatty acid
-
?

Synonyms

Synonyms Comment Organism
DAGLalpha
-
Homo sapiens
diacylglycerol lipase
-
Homo sapiens

Expression

Organism Comment Expression
Homo sapiens DAGLalpha expression is dramatically downregulated when neural stem (NS) cells are differentiated toward a gamma-aminobutyric acidergic neuronal phenotype. Like DAGLalpha, Sp1 is downregulated during neuronal differentiation. The dnSp1 significantly decreases the luciferase activity of P6 relative to GC-box-deleted P6. DAGLalpha expression is dynamically regulated in Cor-1 cells, being dramatically downregulated when the cells are differentiated toward a GABAergic neuronal phenotype. DAGLalpha protein is downregulated in Cor-1 cells during neuronal differentiation down
Homo sapiens the core DAGLa promoter is under a different regulatory control in the different cell types and identify two independent elements that can specifically regulate expression in Cor-1 cells. The GC-box is required for DAGLa core promoter activity in Cor-1 cells but not in 3T3 cells additional information

General Information

General Information Comment Organism
malfunction DAGLalpha expression is dramatically downregulated when neural stem (NS) cells are differentiated toward a gamma-aminobutyric acidergic neuronal phenotype. Specific mutation within the GCbox that inhibits Sp1 binding reduced DAGLalpha promoter activity in NS cells. A dominant negative Sp1 is shown to bind to the GC-box and to suppress DAGLalpha promoter activity specifically in NS cells. Like DAGLalpha, Sp1 is downregulated during neuronal differentiation Homo sapiens
physiological function the diacylglycerol lipases (DAGLalpha and DAGLbeta) synthesize 2-arachidonoylglycerol (2-AG), a full agonist at cannabinoid receptors. Dynamic regulation of DAGL expression underpins its role in axonal growth and guidance during development, retrograde synaptic signalling at mature synapses, and maintenance of adult neurogenesis. DAGLalpha is expressed in a number of NS cell lines, where it drives cell proliferation via activation of both CB1 and CB2 receptors Homo sapiens