Evidence map›Paper›PMID 27128383›Full record

ArticleACS chemical biology2016

Sequestration-Mediated Downregulation of de Novo Purine Biosynthesis by AMPK.

Danielle L Schmitt, Yun-Ju Cheng, Junyong Park, Songon An

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. A journey into the regulatory secrets of theFrontiers in pharmacology · 2024
    Review
  7. Review
  8. Review
  9. Human de novo purine biosynthesis.Critical reviews in biochemistry and molecular biology · 2021
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Detecting Purinosome Metabolon Formation with Fluorescence Microscopy.Methods in molecular biology (Clifton, N.J.) · 2018
    Article
  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

4 authors at 1 institution in 1 country.

Danielle L SchmittDepartment of Chemistry and Biochemistry, ‡Department of Mathematics and Statistics, University of Maryland Baltimore County (UMBC) , 1000 Hilltop Circle, Baltimore, Maryland 21250, United States.
Yun-Ju ChengDepartment of Chemistry and Biochemistry, ‡Department of Mathematics and Statistics, University of Maryland Baltimore County (UMBC) , 1000 Hilltop Circle, Baltimore, Maryland 21250, United States.
Junyong ParkDepartment of Chemistry and Biochemistry, ‡Department of Mathematics and Statistics, University of Maryland Baltimore County (UMBC) , 1000 Hilltop Circle, Baltimore, Maryland 21250, United States.
Songon AnDepartment of Chemistry and Biochemistry, ‡Department of Mathematics and Statistics, University of Maryland Baltimore County (UMBC) , 1000 Hilltop Circle, Baltimore, Maryland 21250, United States.
University of Maryland, Baltimore County · US

Funding

Graduate Training at The Chemistry Biology InterfaceT32GM066706 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SELEY-RADTKE, KATHERINE L, SMITH, AARON T · 2004 to 2023
$3.3M
NIGMS NIH HHS T32 GM066706
6 · The paper itself

Abstract

Dynamic partitioning of de novo purine biosynthetic enzymes into multienzyme compartments, purinosomes, has been associated with increased flux of de novo purine biosynthesis in human cells. However, we do not know of a mechanism by which de novo purine biosynthesis would be downregulated in cells. We have investigated the functional role of AMP-activated protein kinase (AMPK) in the regulation of de novo purine biosynthesis because of its regulatory action on lipid and carbohydrate biosynthetic pathways. Using pharmacological AMPK activators, we have monitored subcellular localizations of six pathway enzymes tagged with green fluorescent proteins under time-lapse fluorescence single-cell microscopy. We revealed that only one out of six pathway enzymes, formylglycinamidine ribonucleotide synthase (FGAMS), formed spatially distinct cytoplasmic granules after treatment with AMPK activators, indicating the formation of single-enzyme self-assemblies. In addition, subsequent biophysical studies using fluorescence recovery after photobleaching showed that the diffusion kinetics of FGAMS were slower when it localized inside the self-assemblies than within the purinosomes. Importantly, high-performance liquid chromatographic studies revealed that the formation of AMPK-promoted FGAMS self-assembly caused the reduction of purine metabolites in HeLa cells, indicating the downregulation of de novo purine biosynthesis. Collectively, we demonstrate here that the spatial sequestration of FGAMS by AMPK is a mechanism by which de novo purine biosynthesis is downregulated in human cells.

Indexed as

Down-RegulationAMP-Activated Protein KinasesGreen Fluorescent ProteinsHeLa CellsHumansPurinesAMP-Activated Protein Kinasesenhanced green fluorescent proteinGreen Fluorescent ProteinsPurines

Identifiers

PMID27128383
PMCPMC5675104
OpenAlexW2345302670

What OpenQuestion holds

Textmetadata
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.