Evidence map›Paper›PMID 22474248›Full record

ArticleBlood2012

C/EBPα and DEK coordinately regulate myeloid differentiation.

Rositsa I Koleva, Scott B Ficarro, Hanna S Radomska, Marlene J Carrasco-Alfonso, John A Alberta, James T Webber, C John Luckey, Guido Marcucci, Daniel G Tenen, Jarrod A Marto

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 50 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

10 authors at 5 institutions in 2 countries.

Rositsa I KolevaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA.
Scott B Ficarro
Hanna S Radomska
Marlene J Carrasco-Alfonso
John A Alberta
James T Webber
C John Luckey
Guido Marcucci
Daniel G Tenen
Jarrod A Marto
Dana-Farber Cancer Institute · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USHarvard University · USThe Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Transcriptional control of inhibitory synapse formationP01NS047572 · NINDS · DANA-FARBER CANCER INSTITUTE · PI MA, QIUFU · 2004 to 2013
$13.5M
Hematopoietic stem cell commitmentP01DK080665 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 2008 to 2012
$7.3M
Distinct acute myeloid leukemia subclasses with CEBPA mutationsR01CA118316 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 2007 to 2011
$2.0M
NCI NIH HHS CA118316NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA118316NIDDK NIH HHS DK080665NIDDK NIH HHS P01 DK080665NINDS NIH HHS P01 NS047572NINDS NIH HHS P01NS047572
6 · The paper itself

Abstract

The transcription factor C/EBPα is a critical mediator of myeloid differentiation and is often functionally impaired in acute myeloid leukemia. Recent studies have suggested that oncogenic FLT3 activity disrupts wild-type C/EBPα function via phosphorylation on serine 21 (S21). Despite the apparent role of pS21 as a negative regulator of C/EBPα transcription activity, the mechanism by which phosphorylation tips the balance between transcriptionally competent and inhibited forms remains unresolved. In the present study, we used immuno-affinity purification combined with quantitative mass spectrometry to delineate the proteins associated with C/EBPα on chromatin. We identified DEK, a protein with genetic links to leukemia, as a member of the C/EBPα complexes, and demonstrate that this association is disrupted by S21 phosphorylation. We confirmed that DEK is recruited specifically to chromatin with C/EBPα to enhance GCSFR3 promoter activation. In addition, we demonstrated that genetic depletion of DEK reduces the ability of C/EBPα to drive the expression of granulocytic target genes in vitro and disrupts G-CSF-mediated granulocytic differentiation of fresh human BM-derived CD34(+) cells. Our data suggest that C/EBPα and DEK coordinately activate myeloid gene expression and that S21 phosphorylation on wild-type C/EBPα mediates protein interactions that regulate the differentiation capacity of hematopoietic progenitors.

Indexed as

AntibodiesCCAAT-Enhancer-Binding ProteinsCell DifferentiationCells, CulturedChromosomal Proteins, Non-HistoneGene Expression RegulationGene Knockdown TechniquesHEK293 CellsHematopoiesisHumansK562 CellsMAP Kinase Kinase KinasesMyeloid CellsOncogene ProteinsPhosphorylationPoly-ADP-Ribose Binding ProteinsAntibodiesCCAAT-Enhancer-Binding ProteinsCEBPA protein, humanChromosomal Proteins, Non-HistoneDEK protein, humanMAP Kinase Kinase KinasesOncogene ProteinsPoly-ADP-Ribose Binding ProteinsProtein Kinase Inhibitors

Identifiers

PMID22474248
PMCPMC3367892
OpenAlexW2049527989

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.