Evidence map›Paper›PMID 19933706›Full record

ArticleCarcinogenesis2010

NPM phosphorylation stimulates Cdk1, overrides G2/M checkpoint and increases leukemic blasts in mice.

Wei Du, Yun Zhou, Suzette Pike, Qishen Pang

Open access · bronzeAbstract read
In one paragraph

Article in Carcinogenesis, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

11 citing papers in PubMed, 20 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

4 authors at 2 institutions in 1 country.

Wei DuDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Yun Zhou
Suzette Pike
Qishen Pang
Cincinnati Children's Hospital Medical Center · USTexas A&M University · US

Funding

Role of FA Proteins in HematopoiesisR01HL076712 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI PANG, QISHEN · 2005 to 2020
$5.0M
Role of Nucleophosmin in FA-evolved LeukemiaR01CA109641 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI PANG, QISHEN · 2004 to 2008
$1.5M
NCI NIH HHS R01 CA109641NHLBI NIH HHS R01 HL076712
6 · The paper itself

Abstract

An elevated level of nucleophosmin (NPM) is often found in actively proliferative cells including human tumors. To identify the regulatory role for NPM phosphorylation in proliferation and cell cycle control, a series of mutants targeting the consensus cyclin-dependent kinase (CDK) phosphorylation sites was created to mimic or abrogate either single-site or multi-site phosphorylation. Simultaneous inactivation of two CDK phosphorylation sites at Ser10 and Ser70 (NPM-AA) induced G(2)/M cell cycle arrest, phosphorylation of Cdk1 at Tyr15 (Cdc2(Tyr15)) and increased cytoplasmic accumulation of Cdc25C. Strikingly, stress-induced Cdk1(Tyr15) and Cdc25C sequestration was suppressed by expression of a phosphomimetic NPM mutant created on the same CDK sites (S10E/S70E, NPM-EE). Further analysis revealed that phosphorylation of NPM at both Ser10 and Ser70 was required for proper interaction between Cdk1 and Cdc25C. Moreover, NPM-EE directly bound to Cdc25C and prevented phosphorylation of Cdc25C at Ser216 during mitosis. Finally, NPM-EE overrided stress-induced G(2)/M arrest and increased leukemia blasts in a NOD/SCID xenograft model. Thus, these findings reveal a novel function of NPM on regulation of cell cycle progression, in which phosphorylation of NPM controls cell cycle progression at G(2)/M transition through modulation of Cdk1 and Cdc25C activities.

Indexed as

Cell DivisionG2 PhaseAnimalsCDC2 Protein KinaseCell ProliferationImmunoblottingImmunoprecipitationMiceMice, Inbred NODMice, SCIDMitotic IndexNuclear ProteinsNucleophosminPhosphorylationPrecursor Cell Lymphoblastic Leukemia-LymphomaCDC2 Protein KinaseNPM1 protein, humanNuclear ProteinsNucleophosmin

Identifiers

PMID19933706
PMCPMC2812569
OpenAlexW2130802787

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.