9 research outputs found

    Ecology of Juvenile Salmon in Shallow Tidal Freshwater Habitats of the Lower Columbia River, 2007?2010

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    The TFM study was designed to investigate the ecology and early life history of juvenile salmonids within shallow (<5 m) tidal freshwater habitats of the LCRE. We started collecting field data in June 2007. Since then, monthly sampling has occurred in the vicinity of the Sandy River delta (rkm 192–208) and at other sites and times in lower river reaches of tidal freshwater (rkm 110 to 141). This report provides a comprehensive synthesis of data covering the field period from June 2007 through April 2010

    The oncometabolite 2-hydroxyglutarate activates the mTOR signalling pathway

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    The identification of cancer-associated mutations in the tricarboxylic acid (TCA) cycle enzymes isocitrate dehydrogenases 1 and 2 (IDH1/2) highlights the prevailing notion that aberrant metabolic function can contribute to carcinogenesis. IDH1/2 normally catalyse the oxidative decarboxylation of isocitrate into α-ketoglutarate (αKG). In gliomas and acute myeloid leukaemias, IDH1/2 mutations confer gain-of-function leading to production of the oncometabolite R-2-hydroxyglutarate (2HG) from αKG. Here we show that generation of 2HG by mutated IDH1/2 leads to the activation of mTOR by inhibiting KDM4A, an αKG-dependent enzyme of the Jumonji family of lysine demethylases. Furthermore, KDM4A associates with the DEP domain-containing mTOR-interacting protein (DEPTOR), a negative regulator of mTORC1/2. Depletion of KDM4A decreases DEPTOR protein stability. Our results provide an additional molecular mechanism for the oncogenic activity of mutant IDH1/2 by revealing an unprecedented link between TCA cycle defects and positive modulation of mTOR function downstream of the canonical PI3K/AKT/TSC1-2 pathway
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