title: A Late G1 Lipid Checkpoint That Is Dysregulated in Clear Cell Renal Carcinoma Cells.
abstract: Lipids are important nutrients that proliferating cells require to maintain energy homeostasis as well as to build plasma membranes for newly synthesized cells. Previously, we identified nutrient-sensing checkpoints that exist in the latter part of the G1phase of the cell cycle that are dependent upon essential amino acids, Gln, and finally, a checkpoint mediated by mammalian target of rapamycin (mTOR), which integrates signals from both nutrients and growth factors. In this study, we have identified and temporally mapped a lipid-mediated G1checkpoint. This checkpoint is located after the Gln checkpoint and before the mTOR-mediated cell cycle checkpoint. Intriguingly, clear cell renal cell carcinoma cells (ccRCC) have a dysregulated lipid-mediated checkpoint due in part to defective phosphatase and tensin homologue (PTEN). When deprived of lipids, instead of arresting in G1, these cells continue to cycle and utilize lipid droplets as a source of lipids. Lipid droplets have been known to maintain endoplasmic reticulum homeostasis and prevent cytotoxic endoplasmic reticulum stress in ccRCC. Dysregulation of the lipid-mediated checkpoint forces these cells to utilize lipid droplets, which could potentially lead to therapeutic opportunities that exploit this property of ccRCC.
authors.affiliation: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065.|the Biochemistry Program and.
authors.forename: Deven
authors.initials: D
authors.lastname: Patel
authors.affiliation: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065.|Biology Program, Graduate Center of the City University of New York, New York, New York 10016.
authors.forename: Darin
authors.initials: D
authors.lastname: Salloum
authors.affiliation: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065.|the Biochemistry Program and.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Saqcena
authors.affiliation: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065.|Biology Program, Graduate Center of the City University of New York, New York, New York 10016.
authors.forename: Amrita
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065.
authors.forename: Victoria
authors.initials: V
authors.lastname: Mroz
authors.affiliation: the Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Ohh
authors.affiliation: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065, foster@genectr.hunter.cuny.edu.|the Biochemistry Program and.|Biology Program, Graduate Center of the City University of New York, New York, New York 10016.|the Department of Pharmacology, Weill Cornell Medicine, New York, New York 10021, and.
authors.forename: David A
authors.initials: DA
authors.lastname: Foster
mesh_terms: D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D059585:G1 Phase Cell Cycle Checkpoints; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms; D050356:Lipid Metabolism; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D005973:Glutamine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: START; amino acid; cell cycle; checkpoint control; checkpoints; glutamine; lipid; lipids; mTOR complex (mTORC); renal cancer