Evidence map›Paper›PMID 24747950›Full record

ArticleHaematologica2014

Targeted shRNA screening identified critical roles of pleckstrin-2 in erythropoiesis.

Baobing Zhao, Ganesan Keerthivasan, Yang Mei, Jing Yang, James McElherne, Piu Wong, John G Doench, Gang Feng, David E Root, Peng Ji

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

30 citing papers in PubMed, 41 citations in OpenAlex.

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  14. Fine-Tuning of Cholesterol Homeostasis Controls Erythroid Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
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  16. Cancers · 2021
    Article
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  18. Review
  19. Review
  20. Emerging Roles of Pleckstrin-2 Beyond Cell Spreading.Frontiers in cell and developmental biology · 2021
    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

10 authors at 4 institutions in 1 country.

Baobing ZhaoDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Ganesan KeerthivasanDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Yang MeiDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Jing YangDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
James McElherneDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Piu WongWhitehead Institute for Biomedical Research, Cambridge, MA.
John G DoenchBroad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge, MA.
Gang FengBiomedical Informatics Center, Northwestern University, Chicago, IL, USA.
David E RootBroad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge, MA.
Peng JiDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL peng-ji@fsm.northwestern.edu.
Northwestern University · USBroad Institute · USHarvard University · USWhitehead Institute for Biomedical Research · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1)UL1TR000150 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LLOYD-JONES, DONALD M · 2012 to 2013
$10.1M
Analysis of mDia formins in hematopoietic stem cell engraftment and migrationR00HL102154 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI JI, PENG · 2012 to 2014
$720k
NCATS NIH HHS 8UL1TR000150NCATS NIH HHS UL1 TR000150NCI NIH HHS CA060553NCI NIH HHS P30 CA060553NHLBI NIH HHS R00 HL102154NHLBI NIH HHS R00HL102154
6 · The paper itself

Abstract

Differentiation of erythroblasts to mature red blood cells involves dynamic changes of the membrane and cytoskeleton networks that are not fully characterized. Using a mouse fetal liver erythroblast culture system and a targeted shRNA functional screening strategy, we identified a critical role of pleckstrin-2 in actin dynamics and protection of early stage terminal erythroblasts from oxidative damage. Knockdown of pleckstrin-2 in the early stage of terminal erythropoiesis disrupted the actin cytoskeleton and led to differentiation inhibition and apoptosis. This pro-survival and differentiation function of pleckstrin-2 was mediated through its interaction with cofilin, by preventing cofilin's mitochondrial entry when the intracellular level of reactive oxygen species was higher in the early stage of terminal erythropoiesis. Treatment of the cells with a scavenger of reactive oxygen species rescued cofilin's mitochondrial entry and differentiation inhibition induced by pleckstrin-2 knockdown. In contrast, pleckstrin-2 knockdown in late stage terminal erythroblasts had no effect on survival or differentiation but blocked enucleation due to disorganized actin cytoskeleton. Thus, our study identified a dual function of pleckstrin-2 in the early and late stages of terminal erythropoiesis through its regulations of actin dynamics and cofilin's mitochondrial localization, which reflects intracellular level of reactive oxygen species in different developmental stages.

Indexed as

Actin Depolymerizing FactorsActinsAnimalsApoptosisCell DifferentiationErythroblastsErythropoiesisGene Expression ProfilingGene Expression RegulationGenes, ReporterMembrane ProteinsMiceMitochondriaProtein BindingRNA InterferenceRNA, Small InterferingActin Depolymerizing FactorsActinsMembrane ProteinsPlek2 protein, mouseRNA, Small Interfering

Identifiers

PMID24747950
PMCPMC4077076
OpenAlexW2159031057

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.