Evidence map›Paper›PMID 32485148›Full record

ArticleMolecular cell2020

ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis.

Eunus S Ali, Umakant Sahu, Elodie Villa, Brendan P O'Hara, Peng Gao, Cynthia Beaudet, Antony W Wood, John M Asara, Issam Ben-Sahra

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

52 citing papers in PubMed, 70 citations in OpenAlex.

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  15. A high throughput assay for phosphoribosylformylglycinamidine synthase.SLAS discovery : advancing life sciences R & D · 2025
    Article
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  19. Growth Signaling Networks Orchestrate Cancer Metabolic Networks.Cold Spring Harbor perspectives in medicine · 2024
    Review
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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

9 authors at 3 institutions in 1 country.

Eunus S AliDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Umakant SahuDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Elodie VillaDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Brendan P O'HaraDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Peng GaoMetabolomics Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Cynthia BeaudetCell Signaling Technology, Inc., Danvers, MA 01923, USA.
Antony W WoodCell Signaling Technology, Inc., Danvers, MA 01923, USA.
John M AsaraMass Spectrometry Core, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Issam Ben-SahraDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA. Electronic address: issam.ben-sahra@northwestern.edu.
Northwestern University · USCell Signaling Technology (United States) · USHarvard University · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6M
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
Regulation of de novo purine synthesis by the MAPK/ERK pathwayR01GM135587 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BEN-SAHRA, ISSAM · 2020 to 2024
$1.7M
Linking Oncogenic Signaling to Tumor MetabolismR00CA194192 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BEN-SAHRA, ISSAM · 2017 to 2019
$729k
NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA006516NCI NIH HHS R00 CA194192NIGMS NIH HHS R01 GM135587
6 · The paper itself

Abstract

The RAS-ERK/MAPK (RAS-extracellular signal-regulated kinase/mitogen-activated protein kinase) pathway integrates growth-promoting signals to stimulate cell growth and proliferation, at least in part, through alterations in metabolic gene expression. However, examples of direct and rapid regulation of the metabolic pathways by the RAS-ERK pathway remain elusive. We find that physiological and oncogenic ERK signaling activation leads to acute metabolic flux stimulation through the de novo purine synthesis pathway, thereby increasing building block availability for RNA and DNA synthesis, which is required for cell growth and proliferation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation.

Indexed as

A549 CellsAnimalsCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell CycleCell Line, TumorCell ProliferationExtracellular Signal-Regulated MAP KinasesHeLa CellsHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1PhosphorylationPurinesras ProteinsSignal TransductionCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorExtracellular Signal-Regulated MAP KinasesMAPK1 protein, humanMitogen-Activated Protein Kinase 1phosphoribosylformylglycinamidine synthetasePurinesras ProteinscancerERKFGAMMAPKnucleotide synthesisPFASposttranslational modificationpurine metabolismRAStumor growth

Identifiers

PMID32485148
PMCPMC7306006
OpenAlexW3032315367

What OpenQuestion holds

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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.