title: Diacylglycerol kinase epsilon suppresses expression of p53 and glycerol kinase in mouse embryo fibroblasts.
abstract: The incorporation of glycerol into lipid was measured using SV40 transformed mouse embryo fibroblasts (MEFs) from either wild-type (WT) mice or from mice in which the epsilon isoform of diacylglycerol kinase (DGKε) was knocked out (DGKε-/-). We present an explanation for our finding that DGKε-/-MEFs exhibited greater uptake of3H-glycerol into the cell and a greater incorporation into lipids compared with their WT counterparts, with no change in the relative amounts of various lipids between the DGKε-/-and WT MEFs. Glycerol kinase is more highly expressed in the DGKε-/-cells than in their WT counterparts. In addition, the activity of glycerol kinase is greater in the DGKε-/-cells than in their WT counterparts. Other substrates that enter the cell independent of glycerol kinase, such as pyruvate or acetate, are incorporated into lipid to the same extent between DGKε-/-and WT cell lines. We also show that expression of p53, a transcription factor that increases the synthesis of glycerol kinase, is increased in DGKε-/-MEFs in comparison to WT cells. We conclude that the increased incorporation of glycerol into lipids in DGKε-/-cells is a consequence of up-regulation of glycerol kinase and not a result of an increase in the rate of lipid synthesis. Furthermore, increased expression of the pro-survival gene, p53, in cells knocked out for DGKε suggests that cells over-expressing DGKε would have a greater propensity to become tumorigenic.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: So
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Divyanshi
authors.initials: D
authors.lastname: Jalan
authors.affiliation: Nephrology Division & Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Institute of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemaire
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, United States.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Topham
authors.affiliation: Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, DREAM Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada. Electronic address: epand@mcmaster.ca.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
mesh_terms: D000818:Animals; D002460:Cell Line; D019852:Diacylglycerol Kinase / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism*; D005991:Glycerol Kinase / Q000378:metabolism*; D008055:Lipids / Q000502:physiology; D050155:Lipogenesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D008055:Lipids; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D019852:Diacylglycerol Kinase; D005991:Glycerol Kinase; D005990:Glycerol
keywords: Diacylglycerol kinase; Lipid synthesis; Signal transduction; p53