Evidence map›Paper›PMID 23185316›Full record

ArticlePloS one2012

Tissue transglutaminase constitutively activates HIF-1α promoter and nuclear factor-κB via a non-canonical pathway.

Santosh Kumar, Kapil Mehta

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

57 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
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  6. Transglutaminase 2 in breast cancer metastasis and drug resistance.Frontiers in cell and developmental biology · 2024
    Review
  7. Article
  8. High and Low Levels ofInternational journal of molecular sciences · 2023
    Article
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  10. Article
  11. Review
  12. Article
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  15. Article
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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

2 authors at 1 institution in 1 country.

Santosh KumarDepartment of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Kapil Mehta
The University of Texas MD Anderson Cancer Center · US

Funding

Biological and Therapeutic Significance of TG2 in Pancreatic CancerR21CA135218 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MEHTA, KAPIL · 2009 to 2010
$372k
NCI NIH HHS CA135218NCI NIH HHS R21 CA135218
6 · The paper itself

Abstract

Constitutive activation of nuclear factor kappa B (NF-κB) has been linked with carcinogenesis and cancer progression, including metastasis, chemoresistance, and radiation resistance. However, the molecular mechanisms that result in constitutive activation of NF-κB are poorly understood. Here we show that chronic expression of the pro-inflammatory protein tissue transglutaminase (TG2) reprograms the transcription regulatory network in epithelial cells via constitutive activation of NF-κB. TG2-induced NF-κB binds the functional NF-κB binding site in hypoxia-inducible factor-1 (HIF-1α) promoter and results in its increased expression at transcription and protein levels even under normoxic conditions. TG2/NF-κB-induced HIF-1 was deemed essential for increased expression of some transcription repressors, like Zeb1, Zeb2, Snail, and Twist. Unlike tumor necrosis factor-alpha (TNFα), TG2 did not require IκB kinase (IKK) for NF-κB activation. Our data suggest that TG2 binds with IκBα and results in its rapid degradation via a non-proteasomal pathway. Importantly, the catalytically inactive (C277S) mutant form of TG2 was as effective as was wild-type TG2 in activating NF-κB and inducing HIF-1 expression. We also found that TG2 interacted with p65/RelA protein, both in the cytosolic and the nuclear compartment. The TG2/p65(NF-κB) complex binds to the HIF-1 promoter and induced its transcriptional regulation. Inhibition of TG2 or p65/RelA also inhibited the HIF-1α expression and attenuated Zeb1, Zeb2, and Twist expression. To our knowledge, these findings show for the first time a direct link between TG2, NF-κB, and HIF-1α, demonstrating TG2's important role in cancer progression.

Indexed as

Signal TransductionBiocatalysisCell LineChromatin ImmunoprecipitationCross-Linking ReagentsDown-RegulationGTP-Binding ProteinsHumansHypoxia-Inducible Factor 1, alpha SubunitI-kappa B KinaseI-kappa B ProteinsModels, BiologicalNF-kappa BNF-KappaB Inhibitor alphaPromoter Regions, GeneticProteasome Endopeptidase ComplexCross-Linking ReagentsGTP-Binding ProteinsHypoxia-Inducible Factor 1, alpha SubunitI-kappa B KinaseI-kappa B ProteinsNF-kappa BNF-KappaB Inhibitor alphaNFKBIA protein, humanProteasome Endopeptidase ComplexProtein Glutamine gamma Glutamyltransferase 2Repressor ProteinsTransglutaminases

Identifiers

PMID23185316
PMCPMC3501523
OpenAlexW2090142919

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.