title: Arginine starvation in colorectal carcinoma cells: Sensing, impact on translation control and cell cycle distribution.
abstract: Tumor cells rely on a continued exogenous nutrient supply in order to maintain a high proliferative activity. Although a strong dependence of some tumor types on exogenous arginine sources has been reported, the mechanisms of arginine sensing by tumor cells and the impact of changes in arginine availability on translation and cell cycle regulation are not fully understood. The results presented herein state that human colorectal carcinoma cells rapidly exhaust the internal arginine sources in the absence of exogenous arginine and repress global translation by activation of the GCN2-mediated pathway and inhibition of mTOR signaling. Tumor suppressor protein p53 activation and G1/G0 cell cycle arrest support cell survival upon prolonged arginine starvation. Cells with the mutant or deleted TP53 fail to stop cell cycle progression at defined cell cycle checkpoints which appears to be associated with reduced recovery after durable metabolic stress triggered by arginine withdrawal.
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov str., 14/16, Lviv 79005, Ukraine; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Bozhena O
authors.initials: BO
authors.lastname: Vynnytska-Myronovska
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov str., 14/16, Lviv 79005, Ukraine; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Kurlishchuk
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov str., 14/16, Lviv 79005, Ukraine; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Oleh
authors.initials: O
authors.lastname: Chen
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov str., 14/16, Lviv 79005, Ukraine.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Bobak
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dittfeld
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hüther
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Fetscherstr. 74, 01307 Dresden, Germany; Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Leoni A
authors.initials: LA
authors.lastname: Kunz-Schughart
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov str., 14/16, Lviv 79005, Ukraine. Electronic address: stasyk@cellbiol.lviv.ua.
authors.forename: Oleh V
authors.initials: OV
authors.lastname: Stasyk
mesh_terms: D001120:Arginine / Q000378:metabolism*; D002453:Cell Cycle; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D014176:Protein Biosynthesis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D001120:Arginine; D058570:TOR Serine-Threonine Kinases
keywords: Arginine starvation; Colorectal carcinoma; GCN2 pathway; Intracellular arginine level; mTOR signaling; p53 status