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Comment
. 2010 Jun 16;29(12):1946-7.
doi: 10.1038/emboj.2010.110.

How do tumours adapt to nutrient stress?

Ronald C Wek  1 , Kirk A Staschke
Affiliations
Comment

How do tumours adapt to nutrient stress?

Ronald C Wek et al. EMBO J. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
A stressful tumour microenvironment activates GCN2 and PERK and the integrated stress response. A model is shown depicting the activation of GCN2 and PERK eIF2 kinases in response to reduced availability of oxygen, glucose, and amino acids in the tumour microenvironment. Nutrients and oxygen, depicted by the blue gradient, are provided by blood vessels. Activation of PERK and GCN2 phosphorylation of eIF2α leads to lowered global translation, coincident with preferential translation of ATF4 mRNA. Phosphorylation of eIF2α allows for scanning ribosomes to bypass an inhibitory upstream open reading frame in the 5′-leader of the ATF4 mRNA and instead initiate translation at the ATF4-coding region. Elevated levels of ATF4 enhance transcription of genes subject to the ISR including those involved in metabolism, such as asparagine synthetase (ASNS), nutrient uptake, and anti-oxidation. ATF4 also enhances transcription of GADD34, which participates in the feedback dephosphorylation of eIF2α.
See this image and copyright information in PMC

Comment on

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