Evidence map›Paper›PMID 19247369›Full record

ArticleCell death and differentiation2009

Hdm2 is a ubiquitin ligase of Ku70-Akt promotes cell survival by inhibiting Hdm2-dependent Ku70 destabilization.

V Gama, J A Gomez, L D Mayo, M W Jackson, D Danielpour, K Song, A L Haas, M J Laughlin, S Matsuyama

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

33 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
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  4. Article
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  6. Review
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  8. Review
  9. Article
  10. Induction of deubiquitinating enzyme USP50 during erythropoiesis and its potential role in the regulation of Ku70 stability.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2018
    Article
  11. Article
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  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. MDM2's social network.Oncogene · 2014
    Review
  19. Article
  20. Review
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

9 authors at 3 institutions in 1 country.

V GamaDepartment of Medicine, Division of Hematology-Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
J A Gomez
L D Mayo
M W Jackson
D Danielpour
K Song
A L Haas
M J Laughlin
S Matsuyama
Case Western Reserve University · USIndiana University – Purdue University Indianapolis · USLouisiana State University · US

Funding

Bax Activation Mechanism in the CytosolR01AG031903 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI MATSUYAMA, SHIGEMI · 2008 to 2012
$1.4M
NIA NIH HHS R01 AG031903NIA NIH HHS R01AG031903
6 · The paper itself

Abstract

Earlier, we have reported that 70 kDa subunit of Ku protein heterodimer (Ku70) binds and inhibits Bax activity in the cytosol and that ubiquitin (Ub)-dependent proteolysis of cytosolic Ku70 facilitates Bax-mediated apoptosis. We found that Hdm2 (human homolog of murine double minute) has an ability to ubiquitinate Ku70 and that Hdm2 overexpression in cultured cells causes a decrease in Ku70 expression levels. An interaction between Ku70 and Hdm2 was shown by means of immunoprecipitation, whereas none could be shown between 80 kDa subunit of Ku protein heterodimer and Hdm2. Vascular endothelial growth factor (VEGF) is known to inhibit endothelial cell (EC) apoptosis through an Akt-mediated survival kinase signal; however, the mechanism underlying this inhibition of apoptosis has not been fully elucidated. We found that VEGF inhibited cytosolic Ku70 degradation induced by apoptotic stress. It is known that Akt-dependent phosphorylation of Hdm2 causes nuclear translocation of Hdm2 followed by Hdm2-mediated inactivation of p53. We found that VEGF stimulated nuclear translocation of Hdm2 in EC and efficiently inhibited Ku70 degradation. We also found that constitutively active Akt, but not kinase-dead Akt, inhibited Ku70 degradation in the cytosol. Furthermore, Ku70 knockdown diminished antiapoptotic activity of Akt. Taken together, we propose that Hdm2 is a Ku70 Ub ligase and that Akt inhibits Bax-mediated apoptosis, at least in part, by maintaining Ku70 levels through the promotion of Hdm2 nuclear translocation.

Indexed as

Antigens, NuclearApoptosisbcl-2-Associated X ProteinCell LineCell SurvivalDNA-Binding ProteinsHeLa CellsHumansKu AutoantigenPhosphorylationProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mdm2RNA, Small InterferingTumor Suppressor Protein p53UbiquitinationVascular Endothelial Growth Factor AAntigens, Nuclearbcl-2-Associated X ProteinDNA-Binding ProteinsKu AutoantigenMDM2 protein, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mdm2RNA, Small InterferingTumor Suppressor Protein p53Vascular Endothelial Growth Factor AXrcc6 protein, human

Identifiers

PMID19247369
PMCPMC2669846
OpenAlexW1974851152

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.