Evidence map›Paper›PMID 15509798›Full record

ArticleMolecular and cellular biology2004

NAD+ modulates p53 DNA binding specificity and function.

Kevin G McLure, Masatoshi Takagi, Michael B Kastan

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

32 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. CNature communications · 2018
    Article
  15. Article
  16. Article
  17. Review
  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

3 authors at 1 institution in 1 country.

Kevin G McLureDepartment of Hematology-Oncology, St. Jude Children's Research Hospital, Room D-5048, 332 N. Lauderdale St., Memphis, TN 38105-2794, USA.
Masatoshi Takagi
Michael B Kastan
St. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Cellular Stress Response Signaling PathwaysR37ES005777 · NIEHS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KASTAN, MICHAEL B · 2002 to 2011
$3.7M
ROLE OF P53 IN THE CELLULAR RESPONSE TO DNA DAMAGER01ES005777 · NIEHS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KASTAN, MICHAEL B · 1992 to 2017
$2.3M
NCI NIH HHS CA21765NCI NIH HHS P30 CA021765NIEHS NIH HHS ES05777NIEHS NIH HHS R01 ES005777NIEHS NIH HHS R37 ES005777
6 · The paper itself

Abstract

DNA damage induces p53 DNA binding activity, which affects tumorigenesis, tumor responses to therapies, and the toxicities of cancer therapies (B. Vogelstein, D. Lane, and A. J. Levine, Nature 408:307-310, 2000; K. H. Vousden and X. Lu, Nat. Rev. Cancer 2:594-604, 2002). Both transcriptional and transcription-independent activities of p53 contribute to DNA damage-induced cell cycle arrest, apoptosis, and aneuploidy prevention (M. B. Kastan et al., Cell 71:587-597, 1992; K. H. Vousden and X. Lu, Nat. Rev. Cancer 2:594-604, 2002). Small-molecule manipulation of p53 DNA binding activity has been an elusive goal, but here we show that NAD(+) binds to p53 tetramers, induces a conformational change, and modulates p53 DNA binding specificity in vitro. Niacinamide (vitamin B(3)) increases the rate of intracellular NAD(+) synthesis, alters radiation-induced p53 DNA binding specificity, and modulates activation of a subset of p53 transcriptional targets. These effects are likely due to a direct effect of NAD(+) on p53, as a molecule structurally related to part of NAD(+), TDP, also inhibits p53 DNA binding, and the TDP precursor, thiamine (vitamin B(1)), inhibits intracellular p53 activity. Niacinamide and thiamine affect two p53-regulated cellular responses to ionizing radiation: rereplication and apoptosis. Thus, niacinamide and thiamine form a novel basis for the development of small molecules that affect p53 function in vivo, and these results suggest that changes in cellular energy metabolism may regulate p53.

Indexed as

Adenosine DiphosphateAnimalsCell LineDNADNA DamageHumansIn Vitro TechniquesMiceMice, Inbred C57BLMice, KnockoutNADNiacinamideProtein BindingProtein ConformationProtein Structure, QuaternaryRecombinant ProteinsAdenosine DiphosphateDNANADNiacinamideRecombinant ProteinsThiamineTumor Suppressor Protein p53

Identifiers

PMID15509798
PMCPMC525472
OpenAlexW2005449470

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.