Restriction of rRNA Synthesis by VHL Maintains Energy Equilibrium under Hypoxia

Mekhail, Karim; Rivero-Lopez, Luis; Khacho, Mireille; Lee, Stephen

doi:10.4161/cc.5.20.3387

Cited by 47 publications

(49 citation statements)

References 64 publications

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“…3D). Previously, it has been reported that acidosis-dependent nucleolar condensation and restriction of rDNA transcription requires nucleolar pVHL (39). We determined the effect of pVHL on rDNA transcription in our system and the results indicate that overexpression of pVHL had little effect on the level of pre-rRNA (supplemental Fig.…”

Section: Resultsmentioning

confidence: 85%

The von Hippel-Lindau Protein pVHL Inhibits Ribosome Biogenesis and Protein Synthesis

Zhao

Zhou

et al. 2013

Journal of Biological Chemistry

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Background: pVHL, a tumor suppressor, functions as the substrate recognition component of an E3-ligase complex that targets hypoxia inducible factor (HIF) 1␣ for destruction. Results: pVHL binds ribosomal protein RPS3, interferes with ribosome assembly, and inhibits protein synthesis. Conclusion: pVHL suppresses ribosome biogenesis and protein synthesis. Significance: The findings disclose a novel function of pVHL and provide insight into the regulation of ribosome biogenesis.

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Section: Resultsmentioning

confidence: 85%

The von Hippel-Lindau Protein pVHL Inhibits Ribosome Biogenesis and Protein Synthesis

Zhao

Zhou

et al. 2013

Journal of Biological Chemistry

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“…Fatty acid synthesis was shown to be favoured by extracellular acidosis through the upregulation of fatty acid synthase [72]. pH i furthermore impacts on cell cycle control [73], ribosome biogenesis [74] and cell death programmes [75,76]. pH i must therefore be regulated within a narrow range to maintain normal cellular function.…”

Section: (I) Hypoxia and Cancer Metabolismmentioning

confidence: 99%

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Andersen

Moreira

Pedersen

2014

Phil. Trans. R. Soc. B

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Major changes in intra-and extracellular pH homoeostasis are shared features of most solid tumours. These changes stem in large part from the metabolic shift of most cancer cells towards glycolytic metabolism and other processes associated with net acid production. In combination with oncogenic signalling and impact from factors in the tumour microenvironment, this upregulates acid-extruding plasma membrane transport proteins which maintain intracellular pH normal or even more alkaline compared with that of normal cells, while in turn acidifying the external microenvironment. Mounting evidence strongly indicates that this contributes significantly to cancer development by favouring e.g. cancer cell migration, invasion and chemotherapy resistance. Finally, while still under-explored, it seems likely that non-cancer cells in the tumour microenvironment also exhibit altered pH regulation and that this may contribute to their malignant properties. Thus, the physical tumour microenvironment and the cancer and stromal cells within it undergo important reciprocal interactions which modulate the tumour pH profile, in turn severely impacting on the course of cancer progression. Here, we summarize recent knowledge of tumour metabolism and the tumour microenvironment, placing it in the context of tumour pH regulation, and discuss how interfering with these properties may be exploited clinically.

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“…49 Acidosis drives a stress response in tumor cells by provoking cell cycle arrest, restricting ribosomal biogenesis (the most energy demanding cellular process) and increasing mitochondrial activity. 50,51 As a result, tumor cells undergo cycles of cellular quiescence and proliferation, depending on nutrient concentrations and pH 52 ( Fig. 2).…”

Section: Tumor Cell Metabolism In Acidosismentioning

confidence: 99%