Evidence map›Paper›PMID 19609947›Full record

ArticleInternational journal of cancer2009

Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt.

Dong Bai, Lynn Ueno, Peter K Vogt

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 292 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
292citing papers in PubMed, 2 pooled it
3.8field-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

292 citing papers in PubMed, 2 syntheses or guidelines pooled it, 518 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
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  17. Cancer management and research · 2026
    Review
  18. Review
  19. Review
  20. Review

232 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

3 authors at 1 institution in 1 country.

Dong BaiThe Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Lynn Ueno
Peter K Vogt
Scripps Research Institute · US

Funding

Small Molecules and Targeted Gene Delivery in Tumor AngiogenesisP01CA078045 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI VOGT, PETER K · 1998 to 2008
$10.2M
P3K, RETROVIRAL ONCOGENE AND HOMOLOG OF PI 3-KINASER01CA078230 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI VOGT, PETER K · 1998 to 2013
$5.6M
NCI NIH HHS P01 CA078045NCI NIH HHS R01 CA078230
6 · The paper itself

Abstract

The serine/threonine kinase Akt (cellular homolog of murine thymoma virus akt8 oncogene), also known as PKB (protein kinase B), is activated by lipid products of phosphatidylinositol 3-kinase (PI3K). Akt phosphorylates numerous protein targets that control cell survival, proliferation and motility. Previous studies suggest that Akt regulates transcriptional activity of the nuclear factor-kappaB (NFkappaB) by inducing phosphorylation and subsequent degradation of inhibitor of kappaB (IkappaB). We show here that NFkappaB-driven transcription increases in chicken embryonic fibroblasts (CEF) transformed by myristylated Akt (myrAkt). Accordingly, both a dominant negative mutant of Akt and Akt inhibitors repress NFkappaB-dependent transcription. The degradation of the IkappaB protein is strongly enhanced in Akt-transformed cells, and the loss of NFkappaB activity by introduction of a super-repressor of NFkappaB, IkappaBSR, interferes with PI3K- and Akt-induced oncogenic transformation of CEF. The phosphorylation of the p65 subunit of NFkappaB at serine 534 is also upregulated in Akt-transformed cells. Our data suggest that the stimulation of NFkappaB by Akt is dependent on the phosphorylation of p65 at S534, mediated by IKK (IkappaB kinase) alpha and beta. Akt phosphorylates IKKalpha on T23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at S534 by IKKalpha and beta. Our results demonstrate two separate functions of the IKK complex in NFkappaB activation in cells with constitutive Akt activity: the phosphorylation and consequent degradation of IkappaB and the phosphorylation of p65. The data further support the conclusion that NFkappaB activity is essential for PI3K- and Akt-induced oncogenic transformation.

Indexed as

Cell Transformation, NeoplasticGene Expression RegulationAnimalsBlotting, WesternCell NucleusChick EmbryoFibroblastsI-kappa B KinaseImmunoprecipitationLuciferasesMiceNF-kappa BPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktSignal TransductionI-kappa B KinaseLuciferasesNF-kappa BPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt

Identifiers

PMID19609947
PMCPMC2767458
OpenAlexW1965627667

What OpenQuestion holds

Textmetadata
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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.