Evidence map›Paper›PMID 24583641›Full record

ArticleCell death and differentiation2014

Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo.

T J Phesse, K B Myant, A M Cole, R A Ridgway, H Pearson, V Muncan, G R van den Brink, K H Vousden, R Sears, L T Vassilev and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

68 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. The Role of BAG3 Protein Interactions in Cardiomyopathies.International journal of molecular sciences · 2024
    Article
  8. Article
  9. Review
  10. Characterization of p53/p63/p73 and Myc expressions during embryogenesis of the sea urchin.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Article
  11. Article
  12. Article
  13. EnhancedScience advances · 2023
    Article
  14. Article
  15. Article
  16. MYC function and regulation in physiological perspective.Frontiers in cell and developmental biology · 2023
    Review
  17. Article
  18. Article
  19. Article
  20. Review

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

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 5 institutions in 3 countries.

T J Phesse1] School of Biosciences, University of Cardiff.CF10 3US, Cardiff, UK [2] Ludwig Institute for Cancer Research, Melbourne, Australia [3] The Walter and Eliza Hall Institute for Medical Research, Melbourne, Australia [4] Department of Medical Biology, University of Melbourne, Melbourne, Australia.
K B MyantBeatson Institute for Cancer Research, Glasgow, UK.
A M ColeBeatson Institute for Cancer Research, Glasgow, UK.
R A RidgwayBeatson Institute for Cancer Research, Glasgow, UK.
H PearsonSchool of Biosciences, University of Cardiff.CF10 3US, Cardiff, UK.
V MuncanDepartment of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
G R van den BrinkDepartment of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
K H VousdenBeatson Institute for Cancer Research, Glasgow, UK.
R SearsDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
L T VassilevDiscovery Oncology, Roche Research Center, Nutley, NJ, USA.
A R ClarkeSchool of Biosciences, University of Cardiff.CF10 3US, Cardiff, UK.
O J SansomBeatson Institute for Cancer Research, Glasgow, UK.
Cancer Research UK Scotland Institute · GBCardiff University · GBLeiden University Medical Center · NLLa Roche College · USOregon Health & Science University · US

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK 12481Cancer Research UK 15937Cancer Research UK 18274
6 · The paper itself

Abstract

Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p53. Mechanistically, this was linked to an upregulation of the E3 Ubiquitin ligase Mdm2, which targets p53 for degradation in c-Myc-deficient intestinal enterocytes. Further, low level overexpression of c-Myc, which does not impact on basal levels of apoptosis, elicited sustained apoptosis in response to DNA damage, suggesting c-Myc activity acts as a crucial cell survival rheostat following DNA damage. We also identify the importance of MYC during DNA damage-induced apoptosis in several other tissues, including the thymus and spleen, using systemic deletion of c-Myc throughout the adult mouse. Together, we have elucidated for the first time in vivo an essential role for endogenous c-Myc in signalling DNA damage-induced apoptosis through the control of the p53 tumour suppressor protein.

Indexed as

AnimalsApoptosisCell SurvivalCisplatinDNA DamageEnterocytesHumansMiceProto-Oncogene Proteins c-mycRadiation, IonizingTumor Suppressor Protein p53CisplatinMyc protein, mouseProto-Oncogene Proteins c-mycTumor Suppressor Protein p53

Identifiers

PMID24583641
PMCPMC4013513
OpenAlexW2051471647

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.