Evidence map›Paper›PMID 38640927›Full record

ArticleDevelopmental cell2024

Sustained ERK signaling promotes G2 cell cycle exit and primes cells for whole-genome duplication.

Adler Guerrero Zuniga, Timothy J Aikin, Connor McKenney, Yovel Lendner, Alain Phung, Paul W Hook, Amy Meltzer, Winston Timp, Sergi Regot

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

Article in Developmental cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Adler Guerrero ZunigaDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Biochemistry, Cellular and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Timothy J AikinDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Biochemistry, Cellular and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Connor McKenneyDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Biochemistry, Cellular and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yovel LendnerDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Alain PhungDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Paul W HookDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA.
Amy MeltzerDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA.
Winston TimpDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA.
Sergi RegotDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: sregot@jhmi.edu.
Johns Hopkins University · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Biochemistry, Cellular and Molecular Biology Program: JHU BioGREAT (Biomedical Graduate REsiliency & Adaptability Training)T32GM144272 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Takanari Inoue · 2022 to 2026
$5.4M
Single Cell Analysis of MAPK Signaling Dynamics in MulticellularityR35GM133499 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Sergi Regot · 2019 to 2026
$3.3M
Causes and Consequences of Whole Genome Duplication in Cancer Progression and Acquired Drug ResistanceR01CA279546 · NCI · JOHNS HOPKINS UNIVERSITY · PI Sergi Regot · 2024 to 2026
$1.4M
NCI NIH HHS R01 CA279546NIGMS NIH HHS R35 GM133499NIGMS NIH HHS T32 GM007445NIGMS NIH HHS T32 GM144272
6 · The paper itself

Abstract

Whole-genome duplication (WGD) is a frequent event in cancer evolution that fuels chromosomal instability. WGD can result from mitotic errors or endoreduplication, yet the molecular mechanisms that drive WGD remain unclear. Here, we use live single-cell analysis to characterize cell-cycle dynamics upon aberrant Ras-ERK signaling. We find that sustained ERK signaling in human cells leads to reactivation of the APC/C in G2, resulting in tetraploid G0-like cells that are primed for WGD. This process is independent of DNA damage or p53 but dependent on p21. Transcriptomics analysis and live-cell imaging showed that constitutive ERK activity promotes p21 expression, which is necessary and sufficient to inhibit CDK activity and which prematurely activates the anaphase-promoting complex (APC/C). Finally, either loss of p53 or reduced ERK signaling allowed for endoreduplication, completing a WGD event. Thus, sustained ERK signaling-induced G2 cell cycle exit represents an alternative path to WGD.

Indexed as

MAP Kinase Signaling SystemTumor Suppressor Protein p53Anaphase-Promoting Complex-CyclosomeCyclin-Dependent Kinase Inhibitor p21DNA DamageG2 PhaseGene DuplicationGenome, HumanHumansAnaphase-Promoting Complex-CyclosomeCyclin-Dependent Kinase Inhibitor p21Tumor Suppressor Protein p53cell cycle dynamicsoncogenesissignaling dynamicswhole-genome duplication

Identifiers

PMID38640927
PMCPMC11233237
OpenAlexW4394913962

What Socratic 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 Socratic graph.