Evidence map›Paper›PMID 39368467›Full record

ArticleCell systems2024

Entrainment and multi-stability of the p53 oscillator in human cells.

Alba Jiménez, Alessandra Lucchetti, Mathias S Heltberg, Liv Moretto, Carlos Sanchez, Ashwini Jambhekar, Mogens H Jensen, Galit Lahav

Abstract read
In one paragraph

Article in Cell systems, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Rhythmic stimulation elicits multiple, concurrent neural responses.Cerebral cortex (New York, N.Y. : 1991) · 2026
    Article
  2. Article
  3. Review
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

8 authors.

Alba JiménezDepartment of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA.
Alessandra LucchettiDepartment of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA; Niels Bohr Institute, University of Copenhagen, Copenhagen 2100, Denmark.
Mathias S HeltbergDepartment of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA; Niels Bohr Institute, University of Copenhagen, Copenhagen 2100, Denmark.
Liv MorettoNiels Bohr Institute, University of Copenhagen, Copenhagen 2100, Denmark.
Carlos SanchezDepartment of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA.
Ashwini JambhekarDepartment of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA.
Mogens H JensenNiels Bohr Institute, University of Copenhagen, Copenhagen 2100, Denmark. Electronic address: mhjensen@nbi.ku.dk.
Galit LahavDepartment of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA. Electronic address: galit@hms.harvad.edu.

Funding

Dynamics, Regulation and Function of p53 in Single CellsR35GM139572 · NIGMS · HARVARD MEDICAL SCHOOL · PI Galit Lahav · 2021 to 2026
$4.7M
NIGMS NIH HHS R35 GM139572
6 · The paper itself

Abstract

The tumor suppressor p53 responds to cellular stress and activates transcription programs critical for regulating cell fate. DNA damage triggers oscillations in p53 levels with a robust period. Guided by the theory of synchronization and entrainment, we developed a mathematical model and experimental system to test the ability of the p53 oscillator to entrain to external drug pulses of various periods and strengths. We found that the p53 oscillator can be locked and entrained to a wide range of entrainment modes. External periods far from p53's natural oscillations increased the heterogeneity between individual cells whereas stronger inputs reduced it. Single-cell measurements allowed deriving the phase response curves (PRCs) and multiple Arnold tongues of p53. In addition, multi-stability and non-linear behaviors were mathematically predicted and experimentally detected, including mode hopping, period doubling, and chaos. Our work revealed critical dynamical properties of the p53 oscillator and provided insights into understanding and controlling it. A record of this paper's transparent peer review process is included in the supplemental information.

Indexed as

Tumor Suppressor Protein p53DNA DamageHumansModels, BiologicalModels, TheoreticalSingle-Cell AnalysisTP53 protein, humanTumor Suppressor Protein p53Arnold tonguesentrainmentfrequencyimagingoscillationsp53periodPRCresettingsingle cellssynchrony

Identifiers

PMID39368467
PMCPMC11894796

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.