Evidence map›Paper›PMID 18644867›Full record

ArticleMolecular and cellular biology2008

Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells.

Irit Carmi-Levy, Nurit Yannay-Cohen, Gillian Kay, Ehud Razin, Hovav Nechushtan

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

22 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The pLysRS-ApInternational journal of molecular sciences · 2021
    Review
  5. Article
  6. Article
  7. Review
  8. Re-evaluation of Diadenosine Tetraphosphate (ApFrontiers in molecular biosciences · 2020
    Review
  9. Review
  10. Second messenger ApNature communications · 2019
    Article
  11. MITF-the first 25 years.Genes & development · 2019
    Review
  12. ApiScience · 2019
    Article
  13. Article
  14. Article
  15. Article
  16. Crystal structure of wild-type and mutant human Ap4A hydrolase.Biochemical and biophysical research communications · 2013
    Article
  17. Article
  18. Article
  19. Article
  20. 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 2 institutions in 1 country.

Irit Carmi-LevyDepartment of Biochemistry, Hebrew University Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel.
Nurit Yannay-Cohen
Gillian Kay
Ehud Razin
Hovav Nechushtan
Hebrew University of Jerusalem · ILHadassah Medical Center · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We previously discovered that microphthalmia transcription factor (MITF) and upstream stimulatory factor 2 (USF2) each forms a complex with its inhibitor histidine triad nucleotide-binding 1 (Hint-1) and with lysyl-tRNA synthetase (LysRS). Moreover, we showed that the dinucleotide diadenosine tetraphosphate (Ap(4)A), previously shown to be synthesized by LysRS, binds to Hint-1, and as a result the transcription factors are released from their suppression. Thus, transcriptional activity is regulated by Ap(4)A, suggesting that Ap(4)A is a second messenger in this context. For Ap(4)A to be unambiguously established as a second messenger, several criteria have to be fulfilled, including the presence of a metabolizing enzyme. Since several enzymes are able to hydrolyze Ap(4)A, we provided here evidence that the "Nudix" type 2 gene product, Ap(4)A hydrolase, is responsible for Ap(4)A degradation following the immunological activation of mast cells. The knockdown of Ap(4)A hydrolase modulated Ap(4)A accumulation, resulting in changes in the expression of MITF and USF2 target genes. Moreover, our observations demonstrated that the involvement of Ap(4)A hydrolase in gene regulation is not a phenomenon exclusive to mast cells but can also be found in cardiac cells activated with the beta-agonist isoproterenol. Thus, we have provided concrete evidence establishing Ap(4)A as a second messenger in the regulation of gene expression.

Indexed as

Gene Regulatory NetworksTranscription, GeneticAcid Anhydride HydrolasesAdrenergic beta-AgonistsAnimalsCarrier ProteinsCell LineDinucleoside PhosphatesHydrolasesIsoproterenolLysine-tRNA LigaseMast CellsMicrophthalmia-Associated Transcription FactorMyocytes, CardiacRatsRNA, Small InterferingAcid Anhydride HydrolasesAdrenergic beta-Agonistsbis(5'-nucleosyl)tetraphosphatase (asymmetrical)Carrier Proteinsdiadenosine tetraphosphateDinucleoside Phosphateshistidine triad nucleotide-binding protein, mammalsHydrolasesIsoproterenolLysine-tRNA LigaseMicrophthalmia-Associated Transcription FactorRNA, Small InterferingUpstream Stimulatory Factors

Identifiers

PMID18644867
PMCPMC2546939
OpenAlexW2115998200

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.