Evidence map›Paper›PMID 18803232›Full record

ArticleJournal of cellular physiology2009

Sustained NF-kappaB activation produces a short-term cell proliferation block in conjunction with repressing effectors of cell cycle progression controlled by E2F or FoxM1.

Marianna Penzo, Paul E Massa, Eleonora Olivotto, Francesca Bianchi, Rosa Maria Borzi, Adedayo Hanidu, Xiang Li, Jun Li, Kenneth B Marcu

Erratum issuedAbstract read
In one paragraph

Article in Journal of cellular physiology, 2009. 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 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Biological aspects of early osteoarthritis.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2012
    Pooled it
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Marianna PenzoCentro Ricerca Biomedica Applicata (CRBA), S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
Paul E Massa
Eleonora Olivotto
Francesca Bianchi
Rosa Maria Borzi
Adedayo Hanidu
Xiang Li
Jun Li
Kenneth B Marcu
Boehringer Ingelheim (United States) · USIstituto Ortopedico Rizzoli · ITPoliclinico S.Orsola-Malpighi · ITUniversity of Bologna · ITVita-Salute San Raffaele University · IT

Funding

Novel roles of IKK complex to program gene expressionR01GM066882 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI MARCU, KENNETH B · 2003 to 2006
$1.3M
NIGMS NIH HHS GM-066882NIGMS NIH HHS R01 GM066882
6 · The paper itself

Abstract

NF-kappaB transcription factors induce a host of genes involved in pro-inflammatory/stress-like responses; but the collateral effects and consequences of sustained NF-kappaB activation on other cellular gene expression programming remain less well understood. Here enforced expression of a constitutively active IKKbeta T-loop mutant (IKKbetaca) drove murine fibroblasts into transient growth arrest that subsided within 2-3 weeks of continuous culture. Proliferation arrest was associated with a G1/S phase block in immortalized and primary early passage MEFs. Molecular analysis in immortalized MEFs revealed that inhibition of cell proliferation in the initial 1-2 weeks after their IKKbetaca retroviral infection was linked to the transient, concerted repression of essential cell cycle effectors that are known targets of either E2F or FoxM1. Co-expression of a phosphorylation resistant IkappaBalpha super repressor and IKKbetaca abrogated growth arrest and cell cycle effector repression, thereby linking IKKbetaca's effects to canonical NF-kappaB activation. Transient growth arrest of IKKbetaca cells was associated with enhanced p21 (cyclin-dependent kinase inhibitor 1A) protein expression, due in part to transcriptional activation by NF-kappaB and also likely due to strong repression of Skp2 and Csk1, both of which are FoxM1 direct targets mediating proteasomal dependent p21 turnover. Ablation of p21 in immortalized MEFs reduced their IKKbetaca mediated growth suppression. Moreover, trichostatin A inhibition of HDACs alleviated the repression of E2F and FoxM1 targets induced by IKKbetaca, suggesting chromatin mediated gene silencing in IKKbetaca's short term repressive effects on E2F and FoxM1 target gene expression.

Indexed as

Cell ProliferationAnimalsBase SequenceCell CycleCells, CulturedCyclin-Dependent Kinase Inhibitor p21DNA PrimersE2F Transcription FactorsForkhead Box Protein M1Forkhead Transcription FactorsGene SilencingHistone DeacetylasesI-kappa B KinaseI-kappa B ProteinsIntracellular Signaling Peptides and ProteinsMiceChuk protein, mouseCyclin-Dependent Kinase Inhibitor p21DNA PrimersE2F Transcription FactorsForkhead Box Protein M1Forkhead Transcription FactorsFoxm1 protein, mouseHistone DeacetylasesI-kappa B KinaseI-kappa B ProteinsIkbkb protein, mouseIntracellular Signaling Peptides and ProteinsNEMO protein, mouseNF-kappa BNF-KappaB Inhibitor alphaNfkbia protein, mouseRepressor Proteins

Identifiers

PMID18803232
PMCPMC2581928
OpenAlexW2145849766

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.