Evidence map›Paper›PMID 18003885›Full record

ArticleBlood2008

Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation.

Linsheng Zhang, Florence B Fried, Hong Guo, Alan D Friedman

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing 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

40 citing papers in PubMed, 66 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 1 institution in 1 country.

Linsheng ZhangDivision of Pediatric Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
Florence B Fried
Hong Guo
Alan D Friedman
Johns Hopkins University · US

Funding

Cell Cycle Regulation and Leukemogenesis by CBFb-SMMHCR01CA098805 · NCI · JOHNS HOPKINS UNIVERSITY · PI FRIEDMAN, ALAN D · 2003 to 2007
$1.6M
NCI NIH HHS CA098805NCI NIH HHS R01 CA098805
6 · The paper itself

Abstract

RUNX1/AML1 regulates lineage-specific genes during hematopoiesis and stimulates G1 cell-cycle progression. Within RUNX1, S48, S303, and S424 fit the cyclin-dependent kinase (cdk) phosphorylation consensus, (S/T)PX(R/K). Phosphorylation of RUNX1 by cdks on serine 303 was shown to mediate destabilization of RUNX1 in G2/M. We now use an in vitro kinase assay, phosphopeptide-specific antiserum, and the cdk inhibitor roscovitine to demonstrate that S48 and S424 are also phosphorylated by cdk1 or cdk6 in hematopoietic cells. S48 phosphorylation of RUNX1 paralleled total RUNX1 levels during cell-cycle progression, S303 was more effectively phosphorylated in G2/M, and S424 in G1. Single, double, and triple mutation of the cdk sites to the partially phosphomimetic aspartic acid mildly reduced DNA affinity while progressively increasing transactivation of a model reporter. Mutation to alanine increased DNA affinity, suggesting that in other gene or cellular contexts phosphorylation of RUNX1 by cdks may reduce transactivation. The tripleD RUNX1 mutant rescued Ba/F3 cells from inhibition of proliferation by CBFbeta-SMMHC more effectively than the tripleA mutant. Together these findings indicate that cdk phosphorylation of RUNX1 potentially couples stem/progenitor proliferation and lineage progression.

Indexed as

CDC2 Protein KinaseCell LineCell ProliferationCore Binding Factor Alpha 3 SubunitCyclin-Dependent Kinase 6HumansPhosphorylationPhosphoserineTranscriptional ActivationCDC2 Protein KinaseCore Binding Factor Alpha 3 SubunitCyclin-Dependent Kinase 6PhosphoserineRunx3 protein, human

Identifiers

PMID18003885
PMCPMC2214750
OpenAlexW1979431731

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.