{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nofal M"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["158-172.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8961722"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(2)"],"pubmed_abstract":["Pancreatic cancer cells with limited access to free amino acids can grow by scavenging extracellular protein. In a murine model of pancreatic cancer, we performed a genome-wide CRISPR screen for genes required for scavenging-dependent growth. The screen identified key mediators of macropinocytosis, peripheral lysosome positioning, endosome-lysosome fusion, lysosomal protein catabolism, and translational control. The top hit was GCN2, a kinase that suppresses translation initiation upon amino acid depletion. Using isotope tracers, we show that GCN2 is not required for protein scavenging. Instead, GCN2 prevents ribosome stalling but without slowing protein synthesis; cells still use all of the limiting amino acids as they emerge from lysosomes. GCN2 also adapts gene expression to the nutrien"],"journal":["Cell systems"],"pubmed_title":["GCN2 adapts protein synthesis to scavenging-dependent growth."],"pmcid":["PMC8961722"],"funding_grant_id":["R01 DK109714","R35 GM128813","T32 GM007388","DP1 AI124669","DP1 DK113643","F31 CA186513","R01 CA163591"],"pubmed_authors":["Rabinowitz JD","Wuhr M","Gitai Z","Yang L","Nofal M","Parsons L","Han S","Jankowski CSR","Sabatini DM","Wang T","Frese AN","Anthony TG","Hsin-Jung Li S"],"additional_accession":[]},"is_claimable":false,"name":"GCN2 adapts protein synthesis to scavenging-dependent growth.","description":"Pancreatic cancer cells with limited access to free amino acids can grow by scavenging extracellular protein. In a murine model of pancreatic cancer, we performed a genome-wide CRISPR screen for genes required for scavenging-dependent growth. The screen identified key mediators of macropinocytosis, peripheral lysosome positioning, endosome-lysosome fusion, lysosomal protein catabolism, and translational control. The top hit was GCN2, a kinase that suppresses translation initiation upon amino acid depletion. Using isotope tracers, we show that GCN2 is not required for protein scavenging. Instead, GCN2 prevents ribosome stalling but without slowing protein synthesis; cells still use all of the limiting amino acids as they emerge from lysosomes. GCN2 also adapts gene expression to the nutrien","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-05-09T13:39:37.551Z","creation":"2025-04-04T08:01:35.985Z"},"accession":"S-EPMC8961722","cross_references":{"pubmed":["34706266"],"doi":["10.1016/j.cels.2021.09.014"]}}