Evidence map›Paper›PMID 19435876›Full record

ArticleMolecular cancer therapeutics2009

NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III(1).

Thomas S Dexheimer, Steven S Carey, Song Zuohe, Vijay M Gokhale, Xiaohui Hu, Lauren B Murata, Estelle M Maes, Andrzej Weichsel, Daekyu Sun, Emmanuelle J Meuillet and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

47 citing papers in PubMed, 101 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. NME/NM23/NDPK and Histidine Phosphorylation.International journal of molecular sciences · 2020
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Nuclear functions of NME proteins.Laboratory investigation; a journal of technical methods and pathology · 2018
    Review
  14. CSGID Solves Structures and Identifies Phenotypes for Five Enzymes inFrontiers in cellular and infection microbiology · 2018
    Article
  15. Small molecule selectively suppresses MYC transcription in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. 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

12 authors at 2 institutions in 2 countries.

Thomas S DexheimerCollege of Pharmacy,University of Arizona, Tucson, Arizona 85721, USA.
Steven S Carey
Song Zuohe
Vijay M Gokhale
Xiaohui Hu
Lauren B Murata
Estelle M Maes
Andrzej Weichsel
Daekyu Sun
Emmanuelle J Meuillet
William R Montfort
Laurence H Hurley
University of Arizona · USInstitute of Pharmacology · CZ

Funding

SPORE in Gastrointestinal CancerP50CA095060 · NCI · UNIVERSITY OF ARIZONA · PI GERNER, EUGENE W · 2002 to 2012
$25.3M
X-RAY STUDY OF HORMONE-RECEPTOR AND PROTEIN-ANTIBODY COMPLEXESP41RR007707 · NCRR · UNIVERSITY OF CHICAGO · PI YANG, XIANGZHONG · 2002 to 2011
$17.3M
SALIVARY PROTEINS FROM BLOOD-SUCKING INSECTSR01HL062969 · NHLBI · UNIVERSITY OF ARIZONA · PI MONTFORT, WILLIAM R. · 2000 to 2012
$3.4M
G-Quadruplexes as Targets for Drug DesignR01CA094166 · NCI · UNIVERSITY OF ARIZONA · PI HURLEY, LAURENCE H. · 2002 to 2007
$1.8M
NCI NIH HHS CA94166NCI NIH HHS P50 CA095060NCI NIH HHS R01 CA094166NCRR NIH HHS P41 RR007707NCRR NIH HHS RR07707NHLBI NIH HHS HL62969NHLBI NIH HHS R01 HL062969
6 · The paper itself

Abstract

The formation of G-quadruplex structures within the nuclease hypersensitive element (NHE) III(1) region of the c-myc promoter and the ability of these structures to repress c-myc transcription have been well established. However, just how these extremely stable DNA secondary structures are transformed to activate c-myc transcription is still unknown. NM23-H2/nucleoside diphosphate kinase B has been recognized as an activator of c-myc transcription via interactions with the NHE III(1) region of the c-myc gene promoter. Through the use of RNA interference, we confirmed the transcriptional regulatory role of NM23-H2. In addition, we find that further purification of NM23-H2 results in loss of the previously identified DNA strand cleavage activity, but retention of its DNA binding activity. NM23-H2 binds to both single-stranded guanine- and cytosine-rich strands of the c-myc NHE III(1) and, to a lesser extent, to a random single-stranded DNA template. However, it does not bind to or cleave the NHE III(1) in duplex form. Significantly, potassium ions and compounds that stabilize the G-quadruplex and i-motif structures have an inhibitory effect on NM23-H2 DNA-binding activity. Mutation of Arg(88) to Ala(88) (R88A) reduced both DNA and nucleotide binding but had minimal effect on the NM23-H2 crystal structure. On the basis of these data and molecular modeling studies, we have proposed a stepwise trapping-out of the NHE III(1) region in a single-stranded form, thus allowing single-stranded transcription factors to bind and activate c-myc transcription. Furthermore, this model provides a rationale for how the stabilization of the G-quadruplex or i-motif structures formed within the c-myc gene promoter region can inhibit NM23-H2 from activating c-myc gene expression.

Indexed as

Base SequenceCatalytic DomainCell Line, TumorGene Expression Regulation, NeoplasticGene OrderGenes, mycG-QuadruplexesHumansModels, MolecularMutationNM23 Nucleoside Diphosphate KinasesPromoter Regions, GeneticProtein ConformationRNA InterferenceTranscriptional ActivationNM23 Nucleoside Diphosphate Kinases

Identifiers

PMID19435876
PMCPMC2891668
OpenAlexW2111183115

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Registered trials

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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.