Evidence map›Paper›PMID 18776921›Full record

ArticleOncogene2008

Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly.

W A Braden, A K McClendon, E S Knudsen

RetractedAbstract readRetracted Publication
PubMed Publisher
In one paragraph

Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

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  15. Elevated expression of CDK4 in lung cancer.Journal of translational medicine · 2011
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

W A BradenDepartment of Cancer Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
A K McClendon
E S Knudsen
Sidney Kimmel Cancer Center · USThomas Jefferson University · US

Funding

ENVIRONMETAL CARCINOGENESIS AND MUTAGENESIST32ES007250 · NIEHS · UNIVERSITY OF CINCINNATI · PI MILLER, WILLIAM E · 1988 to 2024
$11.9M
RB-mediated replication controlR01CA106471 · NCI · UNIVERSITY OF CINCINNATI · PI KNUDSEN, ERIK · 2004 to 2008
$1.2M
NCI NIH HHS CA106471NIEHS NIH HHS T32 ES07250-16
6 · The paper itself

Abstract

Cyclin-dependent kinases (CDKs) are important in regulating cell cycle transitions, particularly in coordinating DNA replication. Although the role of CDK2 activity on the replication apparatus has been extensively studied, the role of CDK4/6 in DNA replication control is less understood. Through targeted inhibition of CDK4/6 activity, we demonstrate that CDK4/6 kinase activity promotes cdc6 and cdt1 expression, and pre-replication complex (pre-RC) assembly in cycling cells. Conversely, CDK2 inhibition had no effect on the pre-RC assembly. The inhibition of pre-RC assembly is dependent on a functional retinoblastoma (RB) protein, which mediates downstream effects. As such, CDK4/6 inhibition has minimal effect on the replication apparatus in the absence of RB. The requirement of CDK4/6 was further interrogated using cells lacking D-type cyclins, in which replication complexes form normally, and correspondingly CDK4/6 inhibition had no effect on cell cycle or replication control. However, in the absence of D-type cyclins, CDK2 inhibition resulted in the attenuation of cdc6 and cdt1 levels, suggesting overlapping roles for CDK4/6 and CDK2 in regulating replication protein activity. Finally, CDK4/6 inhibition prevented the accumulation of cdc6 and cdt1 as cells progressed from mitosis through the subsequent G(1). Combined, these studies indicate that CDK4/6 activity is important in regulating the expression of these critical mediators of DNA replication.

Indexed as

Gene Expression Regulation, EnzymologicCell CycleCell Line, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6DNA ReplicationEnzyme InhibitorsG1 PhaseGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHumansMicroscopy, FluorescenceMitosisRetinoblastoma ProteinReverse Transcriptase Polymerase Chain ReactionCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Enzyme InhibitorsRetinoblastoma Protein

Identifiers

PMID18776921
OpenAlexW1968369794

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.