Evidence map›Paper›PMID 9826690›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1998

An artificial cell-cycle inhibitor isolated from a combinatorial library.

B A Cohen, P Colas, R Brent

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.7field-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

31 citing papers in PubMed, 111 citations in OpenAlex.

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  6. Peptide aptamers: development and applications.Current topics in medicinal chemistry · 2015
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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

3 authors at 2 institutions in 2 countries.

B A CohenDepartment of Molecular Biology, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA.
P Colas
R Brent
Molecular Sciences Institute · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding the genetic networks that operate inside cells will require the dissection of interactions among network members. Here we describe a peptide aptamer isolated from a combinatorial library that distinguishes among such interactions. This aptamer binds to cyclin-dependent kinase 2 (Cdk2) and inhibits its kinase activity. In contrast to naturally occurring inhibitors, such as p21(Cip1), which inhibit the activity of Cdk2 on all its substrates, inhibition by pep8 has distinct substrate specificity. We show that the aptamer binds to Cdk2 at or near its active site and that its mode of inhibition is competitive. Expression of pep8 in human cells retards their progression through the G1 phase of the cell cycle. Our results suggest that the aptamer inhibits cell-cycle progression by blocking the activity of Cdk2 on substrates needed for the G1-to-S transition. This work demonstrates the feasibility of selection of artificial proteins to perform functions not developed during evolution. The ability to select proteins that block interactions between a gene product and some partners but not others should make sophisticated genetic manipulations possible in human cells and other currently intractable systems.

Indexed as

CDC2-CDC28 KinasesBinding, CompetitiveCatalytic DomainCell CycleCell LineCloning, MolecularCrosses, GeneticCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsEnzyme InhibitorsG1 PhaseHumansKineticsPeptide LibraryCDC2-CDC28 KinasesCDK2 protein, humanCDKN1A protein, humanCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsEnzyme InhibitorsPeptide LibraryProtein Serine-Threonine KinasesRecombinant Fusion Proteins

Identifiers

PMID9826690
PMCPMC24363
OpenAlexW2050003729

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.