Key Features
Enhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreTumours depend on altered rates of protein synthesis for growth and survival, suggesting that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools and strains energy resources and causes MYC-dependent apoptosis. eIF2B5 limits MYC expression and prevents apoptosis in APC-deficient murine and patient-derived organoids and in APC-deficient murine intestinal epithelia in vivo. Conversely, the high MYC levels present in APC-deficient cells induce phosphorylation of eIF2alpha via the GCN2 and PKR kinases. Pharmacological inhibition of GCN2 phenocopies eIF2B5 depletion and has therapeutic efficacy in tumour organoids, demonstrating that a negative MYC/eIF2alpha feedback loop constitutes a targetable vulnerability of colorectal tumours. SOURCE: Martin EilersMartin Eilers University of Wuerzburg
View on GEOView in PlutoEnhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreUse Pluto's intuitive interface to analyze and visualize data for this experiment. Pluto's platform is equipped with an API & SDKs, making it easy to integrate into your internal bioinformatics processes.
Read about post-pipeline analysisView quality control data and experiment metadata for this experiment.
Request imports from GEO or TCGA directly within Pluto Bio.
Chat with our Scientific Insights team