Evidence map›Paper›PMID 10851069›Full record

ArticleOncogene2000

Exogenous cdk4 overcomes reduced cdk4 RNA and inhibition of G1 progression in hematopoietic cells expressing a dominant-negative CBF - a model for overcoming inhibition of proliferation by CBF oncoproteins.

J Lou, W Cao, F Bernardin, K Ayyanathan, F J RauscherIII, A D Friedman

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2000. 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
3.8field-weighted citation impact, top 6% 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, 56 citations in OpenAlex.

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  17. Fusion-protein truncation provides new insights into leukemogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2004
    Review
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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

6 authors at 1 institution in 1 country.

J LouThe Johns Hopkins Oncology Center, Division of Pediatric Oncology, Baltimore, Maryland, MD 21231, USA.
W Cao
F Bernardin
K Ayyanathan
F J RauscherIII
A D Friedman
The Wistar Institute · US

Funding

TRANSCRIPTIONAL CONTROL IN HEMATOPOIETIC MYELOID CELLSR01HL051388 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI FRIEDMAN, ALAN D · 1995 to 1998
–
NHLBI NIH HHS HL51388
6 · The paper itself

Abstract

Core Binding Factor (CBF) is required for the development of definitive hematopoiesis, and the CBF oncoproteins AML1-ETO, TEL-AML1, and CBFbeta-SMMHC are commonly expressed in subsets of acute leukemia. CBFbeta-SMMHC slows the G1 to S cell cycle transition in hematopoietic cells, but the mechanism of this effect is uncertain. We have sought to determine whether inhibition of CBF-mediated trans-activation is sufficient to slow proliferation. We demonstrate that activation of KRAB-AML1-ER, a protein containing the AML1 DNA-binding domain, the KRAB repression domain, and the Estrogen receptor ligand binding domain, also slows G1, if its DNA-binding domain is intact. Also, exogenous AML1 overcame CBFbeta-SMMHC-induced inhibition of proliferation. Representational difference analysis (RDA) identified cdk4 RNA expression as an early target of KRAB-AML1 activation. Inhibition of CBF activities by KRAB-AML1-ER or CBFbeta-SMMHC rapidly reduced endogenous cdk4 mRNA levels, even in cells proliferating at or near control rates as a result of exogenous cdk4 expression. Over-expression of cdk4, especially a variant which cannot bind p16INK4a, overcame cell cycle inhibition resulting from activation of KRAB-AML1-ER, although cdk4 did not accelerate proliferation when expressed alone. These findings indicate that mutations which alter the expression of G1 regulatory proteins can overcome inhibition of proliferation by CBF oncoproteins. Oncogene (2000).

Indexed as

HematopoiesisNeoplasm ProteinsProto-Oncogene ProteinsAnimalsCell LineCell Transformation, NeoplasticCore Binding Factor Alpha 2 SubunitCore Binding FactorsCyclin-Dependent Kinase 4Cyclin-Dependent KinasesDNA-Binding ProteinsG1 PhaseGene Expression RegulationHematopoietic Stem CellsLeukemiaMiceCBFbeta-MYH11 fusion proteinCdk4 protein, mouseCore Binding Factor Alpha 2 SubunitCore Binding FactorsCyclin-Dependent Kinase 4Cyclin-Dependent KinasesDNA-Binding ProteinsNeoplasm ProteinsOncogene Proteins, FusionProto-Oncogene ProteinsRepressor ProteinsRNARunx1 protein, mouseTranscription Factors

Identifiers

PMID10851069
OpenAlexW2320374658

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.