Evidence map›Paper›PMID 24155332›Full record

ArticleJournal of cell science2014

S-adenosylmethionine limitation induces p38 mitogen-activated protein kinase and triggers cell cycle arrest in G1.

Da-Wei Lin, Benjamin P Chung, Peter Kaiser

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

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

31 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. RNA Sequencing Reveals the Regulation of Betaine on Chicken Myogenesis.Animals : an open access journal from MDPI · 2022
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Targeting the methionine addiction of cancer.American journal of cancer research · 2022
    Review
  17. Review
  18. Review
  19. Review
  20. Review
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

3 authors at 1 institution in 1 country.

Da-Wei LinUniversity of California Irvine, Department of Biological Chemistry, College of Medicine, 240D Med Sci I, Irvine, CA 92697-1700, USA.
Benjamin P Chung
Peter Kaiser
University of California, Irvine · US

Funding

Ubiquitin SignalingR01GM066164 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KAISER, PETER · 2002 to 2022
$7.4M
Regulation by Proteolysis-Independent UbiquitinationR56GM066164 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KAISER, PETER · 2007 to 2007
$265k
NIGMS NIH HHS GM66164NIGMS NIH HHS R01 GM066164NIGMS NIH HHS R56 GM066164
6 · The paper itself

Abstract

The primary methyl group donor S-adenosylmethionine (SAM) is important for a plethora of cellular pathways including methylation of nucleic acids, proteins, and the 5' cap structure of mRNAs, as well as biosynthesis of phospholipids and polyamines. In addition, because it is the cofactor for chromatin methylation, SAM is an important metabolite for the establishment and maintenance of epigenetic marks. Here, we demonstrate that cells halt proliferation when SAM levels become low. Cell cycle arrest occurs primarily in the G1 phase of the cell cycle and is accompanied by activation of the mitogen-activated protein kinase p38 (MAPK14) and subsequent phosphorylation of MAPK-activated protein kinase-2 (MK2). Surprisingly, Cdk4 activity remains high during cell cycle arrest, whereas Cdk2 activity decreases concomitantly with cyclin E levels. Cell cycle arrest was induced by both pharmacological and genetic manipulation of SAM synthesis through inhibition or downregulation of methionine adenosyltransferase, respectively. Depletion of methionine, the precursor of SAM, from the growth medium induced a similar cell cycle arrest. Unexpectedly, neither methionine depletion nor inhibition of methionine adenosyltransferase significantly affected mTORC1 activity, suggesting that the cellular response to SAM limitation is independent from this major nutrient-sensing pathway. These results demonstrate a G1 cell cycle checkpoint that responds to limiting levels of the principal cellular methyl group donor S-adenosylmethionine. This metabolic checkpoint might play important roles in maintenance of epigenetic stability and general cellular integrity.

Indexed as

B-LymphocytesCell Cycle CheckpointsCell Line, TumorCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin EDNA MethylationEpigenesis, GeneticG1 PhaseGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Mechanistic Target of Rapamycin Complex 1MethionineMethionine AdenosyltransferaseCDK2 protein, humanCDK4 protein, humanCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin EIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Mechanistic Target of Rapamycin Complex 1MethionineMethionine AdenosyltransferaseMitogen-Activated Protein Kinase 14Multiprotein ComplexesProtein Serine-Threonine KinasesS-AdenosylmethionineTOR Serine-Threonine KinasesCell cycleMAPKAPK2MK2One carbon cyclep38 MAPKS-adenosylmethionineSAM

Identifiers

PMID24155332
PMCPMC3874783
OpenAlexW2152873736

What OpenQuestion holds

Textmetadata
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.