Evidence map›Paper›PMID 32533938›Full record

ArticleCell systems2020

Quantifying the Central Dogma in the p53 Pathway in Live Single Cells.

Antonina Hafner, José Reyes, Jacob Stewart-Ornstein, Michael Tsabar, Ashwini Jambhekar, Galit Lahav

Open access · bronzeAbstract read
In one paragraph

Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.1field-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

27 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
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  4. Quantifying single-cell responses to irradiation in 3D.Frontiers in bioengineering and biotechnology · 2026
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  19. Inferring gene regulation from stochastic transcriptional variation across single cells at steady state.Proceedings of the National Academy of Sciences of the United States of America · 2022
    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

6 authors at 3 institutions in 1 country.

Antonina HafnerDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
José ReyesDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Jacob Stewart-OrnsteinDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Michael TsabarDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ashwini JambhekarDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Galit LahavDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: galit@hms.harvard.edu.
Harvard University · USCenter for Systems Biology · USBroad Institute · US

Funding

Dynamics of Signaling Pathways: Mechanism and FunctionR01GM083303 · NIGMS · HARVARD MEDICAL SCHOOL · PI LAHAV, GALIT · 2008 to 2020
$5.2M
Dynamics of Cellular Senescence in Single CellsR01GM116864 · NIGMS · HARVARD MEDICAL SCHOOL · PI LAHAV, GALIT · 2017 to 2020
$1.6M
Defining and manipulating quiescence associated DNA damage resistance in single cellsR00CA207727 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STEWART-ORNSTEIN, JACOB · 2019 to 2021
$735k
Defining and manipulating quiescence associated DNA damage resistance in single cellsK99CA207727 · NCI · HARVARD MEDICAL SCHOOL · PI STEWART-ORNSTEIN, JACOB · 2016 to 2017
$332k
NCI NIH HHS K99 CA207727NCI NIH HHS R00 CA207727NIGMS NIH HHS R01 GM083303NIGMS NIH HHS R01 GM116864
6 · The paper itself

Abstract

Transcription factors (TFs) integrate signals to regulate target gene expression, but we generally lack a quantitative understanding of how changes in TF levels regulate mRNA and protein production. Here, we established a system to simultaneously monitor the levels of p53, a TF that shows oscillations following DNA damage, and the transcription and protein levels of its target p21 in individual cells. p21 transcription tracked p53 dynamics, while p21 protein steadily accumulated. p21 transcriptional activation showed bursts of mRNA production, with p53 levels regulating the probability but not magnitude of activation. Variations in p53 levels between cells contributed to heterogeneous p21 transcription while independent p21 alleles exhibited highly correlated behaviors. Pharmacologically elevating p53 increased the probability of p21 transcription with minor effects on its magnitude, leading to a strong increase in p21 protein levels. Our results reveal quantitative mechanisms by which TF dynamics can regulate protein levels of its targets. A record of this paper's transparent peer review process is included in the Supplemental Information.

Indexed as

HumansTranscription FactorsTumor Suppressor Protein p53Transcription FactorsTumor Suppressor Protein p53dynamicsheterogeneityMDM inhibitionp21p53 signalingsingle cellstranscription regulationtranslation

Identifiers

PMID32533938
PMCPMC7413213
OpenAlexW3035653505

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.