Evidence map›Paper›PMID 26228485›Full record

ArticleBlood2015

Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation.

Diamantis G Konstantinidis, Katie M Giger, Mary Risinger, Suvarnamala Pushkaran, Ping Zhou, Phillip Dexheimer, Satwica Yerneni, Paul Andreassen, Ursula Klingmüller, James Palis and 2 more

Open access · greenAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

23 citing papers in PubMed, 34 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

12 authors at 4 institutions in 2 countries.

Diamantis G KonstantinidisCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;ORCID http://orcid.org/0000-0003-3680-0483
Katie M GigerCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;ORCID http://orcid.org/0000-0002-0192-7209
Mary RisingerCollege of Nursing, University of Cincinnati, Cincinnati, OH;
Suvarnamala PushkaranCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;
Ping ZhouCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;
Phillip DexheimerBiomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;
Satwica YerneniBiomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;
Paul AndreassenCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;
Ursula KlingmüllerSystems Biology of Signal Transduction, German Cancer Research Center, Center for Molecular Biology Alliance, Heidelberg, Germany; and.
James PalisDepartment of Pediatrics, Center for Pediatric Biomedical Research, University of Rochester Medical Center, Rochester, NY.
Yi ZhengCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;
Theodosia A KalfaCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH;ORCID http://orcid.org/0000-0002-0426-9686
Cincinnati Children's Hospital Medical Center · USGerman Cancer Research Center · DEUniversity of Cincinnati Medical Center · USUniversity of Rochester Medical Center · US

Funding

Cincinnati Center for Excellence in Molecular HematologyP30DK090971 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2010 to 2015
$4.0M
Ontogeny of erythroid lineage differentiationR01DK071116 · NIDDK · UNIVERSITY OF ROCHESTER · PI PALIS, JAMES · 2006 to 2010
$2.2M
Rho GTPases in Terminal Erythroid MaturationR01HL116352 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KALFA, THEODOSIA ANASTASIOS · 2012 to 2015
$1.5M
NHLBI NIH HHS R01 HL116352NHLBI NIH HHS R01HL116352NIDDK NIH HHS P30 DK 090971NIDDK NIH HHS P30 DK090971NIDDK NIH HHS R01 DK071116
6 · The paper itself

Abstract

RhoA GTPase has been shown in vitro in cell lines and in vivo in nonmammalian organisms to regulate cell division, particularly during cytokinesis and abscission, when 2 daughter cells partition through coordinated actomyosin and microtubule machineries. To investigate the role of this GTPase in the rapidly proliferating mammalian erythroid lineage, we developed a mouse model with erythroid-specific deletion of RhoA. This model was proved embryonic lethal as a result of severe anemia by embryonic day 16.5 (E16.5). The primitive red blood cells were enlarged, poikilocytic, and frequently multinucleated, but were able to sustain life despite experiencing cytokinesis failure. In contrast, definitive erythropoiesis failed and the mice died by E16.5, with profound reduction of maturing erythroblast populations within the fetal liver. RhoA was required to activate myosin-regulatory light chain and localized at the site of the midbody formation in dividing wild-type erythroblasts. Cytokinesis failure caused by RhoA deficiency resulted in p53 activation and p21-transcriptional upregulation with associated cell-cycle arrest, increased DNA damage, and cell death. Our findings demonstrate the role of RhoA as a critical regulator for efficient erythroblast proliferation and the p53 pathway as a powerful quality control mechanism in erythropoiesis.

Indexed as

CytokinesisErythropoiesisActomyosinAnimalsApoptosisCell Cycle CheckpointsDNA DamageEmbryo LossEmbryo, MammalianErythroblastsFemaleGene DeletionMiceMice, Inbred C57BLrhoA GTP-Binding ProteinTumor Suppressor Protein p53ActomyosinrhoA GTP-Binding ProteinTumor Suppressor Protein p53

Identifiers

PMID26228485
PMCPMC4573870
OpenAlexW1647234487

What OpenQuestion holds

Textmetadata
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.