PMID:21074248

Citation	Fang, M, Shen, Z, Huang, S, Zhao, L, Chen, S, Mak, TW and Wang, X (2010) The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143:711-24
Abstract	PI3K and PTEN lipid phosphatase control the level of cellular phosphatidylinositol (3,4,5)-trisphosphate, an activator of AKT kinases that promotes cell growth and survival. Mutations activating AKT are commonly observed in human cancers. We report here that ENTPD5, an endoplasmic reticulum (ER) enzyme, is upregulated in cell lines and primary human tumor samples with active AKT. ENTPD5 hydrolyzes UDP to UMP to promote protein N-glycosylation and folding in ER. Knockdown of ENTPD5 in PTEN null cells causes ER stress and loss of growth factor receptors. ENTPD5, together with cytidine monophosphate kinase-1 and adenylate kinase-1, constitute an ATP hydrolysis cycle that converts ATP to AMP, resulting in a compensatory increase in aerobic glycolysis known as the Warburg effect. The growth of PTEN null cells is inhibited both in vitro and in mouse xenograft tumor models. ENTPD5 is therefore an integral part of the PI3K/PTEN regulatory loop and a potential target for anticancer therapy.
Links	PubMed Online version:10.1016/j.cell.2010.10.010
Keywords	5'-Guanylic Acid/metabolism; Adenosine Triphosphate/metabolism; Aerobiosis; Animals; Cell Line, Tumor; Cell Proliferation; Endoplasmic Reticulum/metabolism; Glycolysis; Glycosylation; Humans; Mice; Neoplasm Transplantation; Oncogene Protein v-akt/metabolism; Oncogene Proteins/genetics; Oncogene Proteins/metabolism; PTEN Phosphohydrolase/genetics; PTEN Phosphohydrolase/metabolism; Pyrophosphatases; Transplantation, Heterologous; Uridine Monophosphate/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ENTP5	located_in	GO:0005783: endoplasmic reticulum	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:ENTP5	involved_in	GO:0014066: regulation of phosphatidylinositol 3-kinase signaling	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ENTP5	enables	GO:0004382: guanosine-diphosphatase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:ENTP5	involved_in	GO:0006487: protein N-linked glycosylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ENTP5	enables	GO:0045134: uridine-diphosphatase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:ENTP5	involved_in	GO:0051084: 'de novo' posttranslational protein folding	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ENTP5	involved_in	GO:0046034: ATP metabolic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ENTP5	involved_in	GO:0045821: positive regulation of glycolytic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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