Evidence map›Paper›PMID 38070134›Full record

ArticleCell reports2023

Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids.

Yao Rong, Alicia M Darnell, Kiera M Sapp, Matthew G Vander Heiden, Sabrina L Spencer

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Big1 is a cell cycle regulator linking cell size to basal body number.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. BRAFbioRxiv : the preprint server for biology · 2024
    Article
  13. The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Article
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

5 authors at 3 institutions in 1 country.

Yao RongDepartment of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
Alicia M DarnellKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kiera M SappKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Matthew G Vander HeidenKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02139, USA.
Sabrina L SpencerDepartment of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA. Electronic address: sabrina.spencer@colorado.edu.
Allen Institute · USUniversity of Colorado Boulder · USBroad Institute · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
TRAINING IN SIGNAL TRANSDUCTION &CELL CYCLE REGULATIONT32GM008759 · NIGMS · UNIVERSITY OF COLORADO AT BOULDER · PI AHN, NATALIE G. · 2000 to 2020
$5.9M
Understanding the role of metabolism in cancerR35CA242379 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2019 to 2025
$5.8M
PROLIFERATION-QUIESCENCE CONTROL IN SINGLE CELLS: INTEGRATION OF MITOGEN, NUTRIENT, AND STRESS SIGNALINGDP2CA238330 · NCI · UNIVERSITY OF COLORADO · PI SPENCER, SABRINA LEIGH · 2018 to 2018
$2.3M
EPA EP-C-18-008NCI NIH HHS DP2 CA238330NCI NIH HHS P30 CA014051NCI NIH HHS R35 CA242379NIGMS NIH HHS T32 GM008759
6 · The paper itself

Abstract

Amino acids are required for cell growth and proliferation, but it remains unclear when and how amino acid availability impinges on the proliferation-quiescence decision. Here, we used time-lapse microscopy and single-cell tracking of cyclin-dependent kinase 2 (CDK2) activity to assess the response of individual cells to withdrawal of single amino acids and found strikingly different cell-cycle effects depending on the amino acid. For example, upon leucine withdrawal, MCF10A cells complete two cell cycles and then enter a CDK2-low quiescence, whereas lysine withdrawal causes immediate cell-cycle stalling. Methionine withdrawal triggers a restriction point phenotype similar to serum starvation or Mek inhibition: upon methionine withdrawal, cells complete their current cell cycle and enter a CDK2-low quiescence after mitosis. Modulation of restriction point regulators p21/p27 or cyclin D1 enables short-term rescue of proliferation under methionine and leucine withdrawal, and to a lesser extent lysine withdrawal, revealing a checkpoint connecting nutrient signaling to cell-cycle entry.

Indexed as

CDC2-CDC28 KinasesCell Cycle ProteinsAmino AcidsCell CycleCell Cycle CheckpointsCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent Kinase Inhibitor p27Cyclin-Dependent KinasesLeucineLysineMethionineMitosisAmino AcidsCDC2-CDC28 KinasesCell Cycle ProteinsCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent Kinase Inhibitor p27Cyclin-Dependent KinasesLeucineLysineMethionineamino acid withdrawalCDK2CP: Cell biologycyclin D1leucinelysinemethioninep21p27proliferation-quiescence decisionrestriction point

Identifiers

PMID38070134
PMCPMC11238304
OpenAlexW4389462309

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.