Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Subject: search.filters.subject.Calcium

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  • Article
    Citation - WoS: 49
    Citation - Scopus: 49
    5-Fluorouracil Signaling Through a Calcium-Calmodulin Pathway Is Required for P53 Activation and Apoptosis in Colon Carcinoma Cells
    (Nature Publishing Group, 2013) Can, G.; Akpınar, B.; Baran, Yusuf; Zhivotovsky, B.; Olsson, M.
    5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca 2+) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca 2+ through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca 2+ -chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53 -/- cells confirmed the importance of a Ca 2+ -CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes. © 2013 Macmillan Publishers Limited.
  • Article
    Citation - WoS: 17
    Citation - Scopus: 19
    Nacl Tolerance in Lycopersicon Pennellii Introgression Lines: Qtl Related To Physiological Responses
    (Kluwer Academic Publishers, 2011) Frary, A.; Keleş, D.; Pinar, H.; Göl, D.; Doğanlar, S.
    The growth and ion content of salt sensitive Lycopersicon esculentum Mill. cv. M82 and salt tolerant L. pennellii Correll accession LA716 were examined under both control and stress conditions (150 mM NaCl). L. esculentum grew more vigorously than L. pennellii under optimal conditions, however, L. pennellii was able to maintain its growth better than cultivated tomato when the plants were exposed to salinity. Sodium content of both L. esculentum and L. pennellii increased as a result of NaCl stress. In addition, both species showed reduced potassium and calcium content due to salinity. The physiological traits were also measured in a population of 52 L. pennellii introgression lines grown under both normal and stress conditions. A total of 311 quantitative trait loci (QTL) were identified for the studied traits: plant height, stem diameter, leaf number, leaf and root fresh and dry mass, and sodium, potassium and calcium contents. Some of the loci (124) were identified under both control and stress conditions while 86 QTL were identified only under non-stress conditions and 101 loci were identified only under NaCl stress.