Evidence map›Paper›PMID 24530305›Full record

ArticleMolecular cell2014

Fold change of nuclear NF-κB determines TNF-induced transcription in single cells.

Robin E C Lee, Sarah R Walker, Kate Savery, David A Frank, Suzanne Gaudet

Abstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed
–field-weighted citation impact
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

165 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Autonomous Oscillations of NF-κB.Advances in experimental medicine and biology · 2026
    Review
  6. What makes genes burst.Trends in cell biology · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Direct observation correlates NFκB cRel in B cells with activating and terminating their proliferative program.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article

105 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

5 authors.

Robin E C LeeDepartment of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Sarah R WalkerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Kate SaveryDepartment of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
David A FrankDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Suzanne GaudetDepartment of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: suzanne_gaudet@dfci.harvard.edu.

Funding

Quantitative Analysis of Cell Death Pathways in CancerP01CA139980 · NCI · HARVARD MEDICAL SCHOOL · PI WEISSLEDER, MD, PHD, RALPH · 2010 to 2014
$9.0M
Dual STAT3/NF-kB Inhibitors for Targeted Cancer TherapyR01CA160979 · NCI · DANA-FARBER CANCER INST · PI FRANK, DAVID A. · 2012 to 2016
$1.8M
Single-cell analysis of TNF-induced signaling, transcription and fate decisionsR01GM104247 · NIGMS · DANA-FARBER CANCER INST · PI GAUDET, SUZANNE · 2013 to 2017
$1.7M
CIHRNCI NIH HHS CA139980NCI NIH HHS P01 CA139980NCI NIH HHS R01 CA160979NCI NIH HHS R01-CA160979NIGMS NIH HHS R01 GM104247NIGMS NIH HHS R01-GM104247
6 · The paper itself

Abstract

In response to tumor necrosis factor (TNF), NF-κB enters the nucleus and promotes inflammatory and stress-responsive gene transcription. Because NF-κB deregulation is associated with disease, one might expect strict control of NF-κB localization. However, nuclear NF-κB levels exhibit considerable cell-to-cell variability, even in unstimulated cells. To resolve this paradox and determine how transcription-inducing signals are encoded, we quantified single-cell NF-κB translocation dynamics and transcription in the same cells. We show that TNF-induced transcription correlates best with fold change in nuclear NF-κB, not absolute nuclear NF-κB abundance. Using computational modeling, we find that an incoherent feedforward loop, from competition for binding to κB motifs, could provide memory of the preligand state necessary for fold-change detection. Experimentally, we observed three gene-specific transcriptional patterns that our model recapitulates by modulating competition strength alone. Fold-change detection buffers against stochastic variation in signaling molecules and explains how cells tolerate variability in NF-κB abundance and localization.

Indexed as

Models, StatisticalTranscription, GeneticBinding, CompetitiveBinding SitesCell NucleusComputer SimulationGene Expression RegulationHeLa CellsHumansLigandsMolecular ImagingNF-kappa BProtein BindingProtein Interaction Domains and MotifsProtein TransportRNA, MessengerLigandsNF-kappa BRNA, MessengerTumor Necrosis Factor-alpha

Identifiers

PMID24530305
PMCPMC3977799

What OpenQuestion holds

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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.