Evidence map›Paper›PMID 10671479›Full record

ArticleThe Journal of biological chemistry2000

Fhit-nucleotide specificity probed with novel fluorescent and fluorogenic substrates.

A Draganescu, S C Hodawadekar, K R Gee, C Brenner

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.1field-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

28 citing papers in PubMed, 73 citations in OpenAlex.

  1. Review
  2. Article
  3. Integrated analysis ofCell cycle (Georgetown, Tex.) · 2024
    Review
  4. Fluorescently Labelled ATP Analogues for Direct Monitoring of Ubiquitin Activation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Identification of Fhit as a post-transcriptional effector of Thymidine Kinase 1 expression.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017
    Article
  10. Article
  11. Article
  12. Activity-based probe for histidine kinase signaling.Journal of the American Chemical Society · 2012
    Article
  13. Article
  14. Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2012
    Review
  15. Article
  16. Article
  17. Single-molecule imaging analysis of Ras activation in living cells.Proceedings of the National Academy of Sciences of the United States of America · 2004
    Article
  18. Article
  19. Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled gamma-phosphate-linked GTP analogs.Proceedings of the National Academy of Sciences of the United States of America · 2004
    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

4 authors at 2 institutions in 1 country.

A DraganescuKimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
S C Hodawadekar
K R Gee
C Brenner
Sidney Kimmel Cancer Center · USThomas Jefferson University · US

Funding

Mechanism of Dnmt1 Up-regulation by Fhit LossR01CA075954 · NCI · UNIVERSITY OF IOWA · PI BRENNER, CHARLES M · 1997 to 2012
$3.0M
NCI NIH HHS CA75954NCI NIH HHS R01 CA075954
6 · The paper itself

Abstract

Fhit, a member of the histidine triad superfamily of nucleotide-binding proteins, binds and cleaves diadenosine polyphosphates and functions as a tumor suppressor in human epithelial cancers. Function of Fhit in tumor suppression does not require diadenosine polyphosphate cleavage but correlates with the ability to form substrate complexes. As diadenosine polyphosphates are at lower cellular concentrations than mononucleotides, we sought to quantify interactions between Fhit and competitive inhibitors with the use of diadenosine polyphosphate analogs containing fluorophores in place of one nucleoside. Appp-S-(7-diethylamino-4-methyl-3-(4-succinimidylphenyl)) coumarin (ApppAMC), Appp-S-(4-4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacine-3-yl) methylaminoacetyl (ApppBODIPY), and GpppBODIPY, synthesized in high yield, are effective Fhit substrates, producing AMP or GMP plus fluorophore diphosphates. GpppBODIPY cleavage is accompanied by a 5.4-fold increase in fluorescence because BODIPY fluorescence is quenched by stacking with guanine. Titration of unlabeled diadenosine polyphosphates, inorganic pyrophosphate, mononucleotides, and inorganic phosphate into fluorescent assays provided values of K(m) and K(I) as competitive inhibitors. The data indicate that Fhit discriminates between good substrates via k(cat) and against cellular competitors in equilibrium binding terms. Surprisingly, pyrophosphate competes better than purine mononucleotides.

Indexed as

Acid Anhydride HydrolasesNeoplasm ProteinsAdenine NucleotidesBis(5'-adenosyl)triphosphataseBoron CompoundsFluorescent DyesGuanosine 5'-O-(3-Thiotriphosphate)HumansKineticsMagnetic Resonance SpectroscopyProteins4,4-difluoro-4-bora-3a,4a-diaza-s-indaceneAcid Anhydride HydrolasesAdenine NucleotidesBis(5'-adenosyl)triphosphataseBoron CompoundsFluorescent Dyesguanosine 5'-O-(1-thiotriphosphate)Guanosine 5'-O-(3-Thiotriphosphate)Neoplasm ProteinsProteins

Identifiers

PMID10671479
PMCPMC2556043
OpenAlexW2005674626

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.