Evidence map›Paper›PMID 23055520›Full record

ArticleThe Journal of biological chemistry2012

Dexamethasone partially rescues ataxia telangiectasia-mutated (ATM) deficiency in ataxia telangiectasia by promoting a shortened protein variant retaining kinase activity.

Michele Menotta, Sara Biagiotti, Marzia Bianchi, Luciana Chessa, Mauro Magnani

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02345200 (Body Composition, Muscle Strength and Hormonal Status in Patients With Ataxia Telangiectasia Compared to Healthy Controls), which is not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 19% 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.

NCT02345200 nacompletednot on this mapstarted 2013, after this paper: background citation

Body Composition, Muscle Strength and Hormonal Status in Patients With Ataxia Telangiectasia Compared to Healthy Controls

TypeinterventionalSponsorJohann Wolfgang Goethe University HospitalRan2013 to 2014Enrolled52ConditionsAtaxia TelangiectasiaArmsbioelectrical impedance analysis, blood draw
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants.American journal of physiology. Lung cellular and molecular physiology · 2015
    Trial
  5. Trial
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Dexamethasone induces p21FEBS open bio · 2023
    Article
  18. Article
  19. Article
  20. NADAging cell · 2021
    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.

Michele MenottaDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy. michele.menotta@uniurb.it
Sara Biagiotti
Marzia Bianchi
Luciana Chessa
Mauro Magnani
University of Urbino · ITSapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ataxia telangiectasia (AT) is a rare genetic disease, still incurable, resulting from biallelic mutations in the ataxia telangiectasia-mutated (ATM) gene. Recently, short term treatment with glucocorticoid analogues improved neurological symptoms characteristic of this syndrome. Nevertheless, the molecular mechanism involved in glucocorticoid action in AT patients is not yet known. Here we describe, for the first time in mammalian cells, a short direct repeat-mediated noncanonical splicing event induced by dexamethasone, which leads to the skipping of mutations upstream of nucleotide residue 8450 of ATM coding sequence. The resulting transcript provides an alternative ORF translated in a new ATM variant with the complete kinase domain. This miniATM variant was also highlighted in lymphoblastoid cell lines from AT patients and was shown to be likely active. In conclusion, dexamethasone treatment may partly restore ATM activity in ataxia telangiectasia cells by a new molecular mechanism that overcomes most of the mutations so far described within this gene.

Indexed as

AllelesAlternative SplicingAtaxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell LineCodonCycloheximideDexamethasoneDNA-Binding ProteinsFungal ProteinsGenetic VariationGenotypeGlucocorticoidsHeLa CellsHumansAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsCodonCycloheximideDexamethasoneDNA-Binding ProteinsEndonuclease S1, AspergillusFungal ProteinsGlucocorticoidsPhosphotransferasesProtein Serine-Threonine KinasesProtein Synthesis InhibitorsSingle-Strand Specific DNA and RNA EndonucleasesTumor Suppressor Proteins

Identifiers

PMID23055520
PMCPMC3510833
OpenAlexW1991270874

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.