Nutrient control of TORC1, a cell-cycle regulator

Wang, Xuemin; Proud, Christopher G.

doi:10.1016/j.tcb.2009.03.005

Cited by 178 publications

(162 citation statements)

References 64 publications

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“…One of the targets of AMPK is the master orchestrator of cell growth and proliferation, the mammalian target of rapamycin (mTOR) (Wang and Proud, 2009). mTOR is a kinase that is constitutively active in proliferating cells owing to its activation by the PI3-kinase/Akt pathway.…”

Section: Sensing Glucose Deprivationmentioning

confidence: 99%

Sugar-free approaches to cancer cell killing

et al. 2010

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Tumors show an increased rate of glucose uptake and utilization. For this reason, glucose analogs are used to visualize tumors by the positron emission tomography technique, and inhibitors of glycolytic metabolism are being tested in clinical trials. Upregulation of glycolysis confers several advantages to tumor cells: it promotes tumor growth and has also been shown to interfere with cell death at multiple levels. Enforcement of glycolysis inhibits apoptosis induced by cytokine deprivation. Conversely, antiglycolytic agents enhance cell death induced by radio-and chemotherapy. Synergistic effects are likely due to regulation of the apoptotic machinery, as glucose regulates activation and levels of proapoptotic BH3-only proteins such as Bim, Bad, Puma and Noxa, as well as the antiapoptotic Bcl-2 family of proteins. Moreover, inhibition of glucose metabolism sensitizes cells to death ligands. Glucose deprivation and antiglycolytic drugs induce tumor cell death, which can proceed through necrosis or through mitochondrial or caspase-8-mediated apoptosis. We will discuss how oncogenic pathways involved in metabolic stress signaling, such as p53, AMPK (adenosine monophosphate-activated protein kinase) and Akt/mTOR (mammalian target of rapamycin), influence sensitivity to inhibition of glucose metabolism. Finally, we will analyze the rationale for the use of antiglycolytic inhibitors in the clinic, either as single agents or as a part of combination therapies.

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Section: Sensing Glucose Deprivationmentioning

confidence: 99%

Sugar-free approaches to cancer cell killing

et al. 2010

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“…Recent advances have been made in both yeast and mammals concerning the mechanisms by which amino acids lead to TOR activation. The fundamental mechanism, recruitment of TOR to the lysosomal (vacuolar in yeast) membrane, is conserved between yeast and mammals [36,37]. In yeast, the RAG GTPase Gtr1 interacts with and activates TOR in the presence of high amino-acid levels [38].…”

Section: Introductionmentioning

confidence: 99%

TOR and ageing: a complex pathway for a complex process

McCormick

Tsai

Kennedy

2011

Phil. Trans. R. Soc. B

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Studies in invertebrate model organisms have led to a wealth of knowledge concerning the ageing process. But which of these discoveries will apply to ageing in humans? Recently, an assessment of the degree of conservation of ageing pathways between two of the leading invertebrate model organisms, Saccharomyces cerevisiae and Caenorhabditis elegans, was completed. The results (i) quantitatively indicated that pathways were conserved between evolutionarily disparate invertebrate species and (ii) emphasized the importance of the TOR kinase pathway in ageing. With recent findings that deletion of the mTOR substrate S6K1 or exposure of mice to the mTOR inhibitor rapamycin result in lifespan extension, mTOR signalling has become a major focus of ageing research. Here, we address downstream targets of mTOR signalling and their possible links to ageing. We also briefly cover other ageing genes identified by comparing worms and yeast, addressing the likelihood that their mammalian counterparts will affect longevity.

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“…Important signal-transduction pathways linking regulation of protein synthesis to nutrient sensing are mitogen-activated protein kinase and target of rapamycin signalling cascades. However, as the connection of these signalling pathways to translational regulation and cell growth has been extensively reviewed, they will not be further discussed here (for more information see reviews [11][12][13][14]). …”

Section: Introductionmentioning

confidence: 99%

Translational regulation of the cell cycle: when, where, how and why?

Kronja

Orr‐Weaver

2011

Phil. Trans. R. Soc. B

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Translational regulation contributes to the control of archetypal and specialized cell cycles, such as the meiotic and early embryonic cycles. Late meiosis and early embryogenesis unfold in the absence of transcription, so they particularly rely on translational repression and activation of stored maternal mRNAs. Here, we present examples of cell cycle regulators that are translationally controlled during different cell cycle and developmental transitions in model organisms ranging from yeast to mouse. Our focus also is on the RNA-binding proteins that affect cell cycle progression by recognizing special features in untranslated regions of mRNAs. Recent research highlights the significance of the cytoplasmic polyadenylation element-binding protein (CPEB). CPEB determines polyadenylation status, and consequently translational efficiency, of its target mRNAs in both transcriptionally active somatic cells as well as in transcriptionally silent mature Xenopus oocytes and early embryos. We discuss the role of CPEB in mediating the translational timing and in some cases spindle-localized translation of critical regulators of Xenopus oogenesis and early embryogenesis. We conclude by outlining potential directions and approaches that may provide further insights into the translational control of the cell cycle.

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Nutrient control of TORC1, a cell-cycle regulator

Cited by 178 publications

References 64 publications

Sugar-free approaches to cancer cell killing

Sugar-free approaches to cancer cell killing

TOR and ageing: a complex pathway for a complex process

Translational regulation of the cell cycle: when, where, how and why?

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