Evidence map›Paper›PMID 24657168›Full record

ArticleMolecular cell2014

Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2.

Feng Rao, Jiyoung Cha, Jing Xu, Risheng Xu, M Scott Vandiver, Richa Tyagi, Robert Tokhunts, Michael A Koldobskiy, Chenglai Fu, Roxanne Barrow and 4 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 129 citations in OpenAlex.

  1. Review
  2. Oncometabolite 5-IPNature chemical biology · 2026
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  4. mBio · 2025
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  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024
    Review
  11. Article
  12. Review
  13. Review
  14. Synthesis and biological evaluation of flavonoid-based IP6K2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Feng RaoThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jiyoung ChaThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jing XuThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Risheng XuThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
M Scott VandiverThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Richa TyagiThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Robert TokhuntsThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Michael A KoldobskiyThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chenglai FuThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Roxanne BarrowThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mingxuan WuDepartment of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Dorothea FiedlerDepartment of Chemistry, Princeton University, Princeton, NJ 08544, USA.
James C BarrowDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Solomon H SnyderThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ssnyder@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USPrinceton University · US

Funding

UNDERSTANDING NO SIGNALING RESULTING IN NEUROPROTECTION.P50DA000266 · NIDA · JOHNS HOPKINS UNIVERSITY · PI WORLEY, PAUL F · 1985 to 2017
$45.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
Thorase Regulation of the Actions of CocaineP50DA044123 · NIDA · JOHNS HOPKINS UNIVERSITY · PI DAWSON, VALINA L., JANAK, PATRICIA H. · 2018 to 2022
$9.0M
NIDA NIH HHS P50 DA000266NIDA NIH HHS P50 DA044123NIGMS NIH HHS T32 GM007309
6 · The paper itself

Abstract

The apoptotic actions of p53 require its phosphorylation by a family of phosphoinositide-3-kinase-related-kinases (PIKKs), which include DNA-PKcs and ATM. These kinases are stabilized by the TTT (Tel2, Tti1, Tti2) cochaperone family, whose actions are mediated by CK2 phosphorylation. The inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (IP7), are generated by a family of inositol hexakisphosphate kinases (IP6Ks), of which IP6K2 has been implicated in p53-associated cell death. In the present study we report an apoptotic signaling cascade linking CK2, TTT, the PIKKs, and p53. We demonstrate that IP7, formed by IP6K2, binds CK2 to enhance its phosphorylation of the TTT complex, thereby stabilizing DNA-PKcs and ATM. This process stimulates p53 phosphorylation at serine 15 to activate the cell death program in human cancer cells and in murine B cells.

Indexed as

ApoptosisAnimalsAtaxia Telangiectasia Mutated ProteinsBinding SitesB-LymphocytesCarrier ProteinsCasein Kinase IIDNA-Activated Protein KinaseDNA-Binding ProteinsEnzyme StabilityHCT116 CellsHEK293 CellsHumansInositol PhosphatesIntracellular Signaling Peptides and ProteinsMice, KnockoutAtaxia Telangiectasia Mutated ProteinsATM protein, humanAtm protein, mouseCarrier ProteinsCasein Kinase IIDNA-Activated Protein KinaseDNA-Binding ProteinsETV7 protein, humaninositol hexakisphosphate kinaseInositol PhosphatesIntracellular Signaling Peptides and ProteinsNuclear ProteinsPhosphotransferases (Phosphate Group Acceptor)PRKDC protein, humanPrkdc protein, mouseProto-Oncogene Proteins c-etsSerineTel2 protein, mouseTelomere-Binding ProteinsTP53 protein, humanTti1 protein, humanTti1 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID24657168
PMCPMC4011022
OpenAlexW2145324729

What OpenQuestion holds

Textmetadata
LicenceTDM
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.