Evidence map›Paper›PMID 34706266›Full record

ArticleCell systems2022

GCN2 adapts protein synthesis to scavenging-dependent growth.

Michel Nofal, Tim Wang, Lifeng Yang, Connor S R Jankowski, Sophia Hsin-Jung Li, Seunghun Han, Lance Parsons, Alexander N Frese, Zemer Gitai, Tracy G Anthony and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Michel NofalLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Tim WangWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Lifeng YangLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Connor S R JankowskiLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Sophia Hsin-Jung LiDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Seunghun HanLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Lance ParsonsLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Alexander N FreseLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Zemer GitaiDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Tracy G AnthonyDepartment of Nutritional Sciences and the New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ 08901, USA.
Martin WührLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
David M SabatiniWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Joshua D RabinowitzLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Ludwig Institute for Cancer Research, Princeton Branch, Princeton University, Princeton, NJ 08540, USA. Electronic address: joshr@princeton.edu.
Princeton University · USRutgers, The State University of New Jersey · US

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007388 · NIGMS · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 1985 to 2022
$27.4M
Tumor cell metabolism in actionR01CA163591 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI JOSHUA D RABINOWITZ, Eileen P. White · 2012 to 2026
$7.0M
Metabolism in Action: Quantitative Fluxes in MammalsDP1DK113643 · NIDDK · PRINCETON UNIVERSITY · PI RABINOWITZ, JOSHUA D · 2016 to 2020
$5.7M
Homeostatic Responses to Amino Acid InsufficiencyR01DK109714 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ANTHONY, TRACY G., WEK, RONALD C · 2016 to 2024
$5.4M
Mechano-microbiology: how physical forces control bacterial-host interactionsDP1AI124669 · NIAID · PRINCETON UNIVERSITY · PI GITAI, ZEMER · 2015 to 2019
$4.0M
Development of New Proteomics Technology and its Application to Study Cellular OrganizationR35GM128813 · NIGMS · PRINCETON UNIVERSITY · PI Martin Wühr · 2018 to 2026
$4.0M
Intact protien as a cancer fuel sourceF31CA186513 · NCI · PRINCETON UNIVERSITY · PI NOFAL, MICHEL · 2014 to 2016
$129k
NCI NIH HHS F31 CA186513NCI NIH HHS R01 CA163591NIAID NIH HHS DP1 AI124669NIDDK NIH HHS DP1 DK113643NIDDK NIH HHS R01 DK109714NIGMS NIH HHS R35 GM128813NIGMS NIH HHS T32 GM007388
6 · The paper itself

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 nutrient-poor environment, reorienting protein synthesis away from ribosomes and toward lysosomal hydrolases, such as cathepsin L. GCN2, cathepsin L, and the other genes identified in the screen are potential therapeutic targets in pancreatic cancer.

Indexed as

Pancreatic NeoplasmsSaccharomyces cerevisiae ProteinsAmino AcidsAnimalsCathepsin LMiceProtein Serine-Threonine KinasesSaccharomyces cerevisiaeAmino AcidsCathepsin LEif2ak4 protein, mouseGCN2 protein, S cerevisiaeProtein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinsCathepsin LGCN2lysosomesmacropinocytosisPDACprotein scavengingprotein synthesistranslation

Identifiers

PMID34706266
PMCPMC8961722
OpenAlexW3210802334

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.