Evidence map›Paper›PMID 21788986›Full record

ArticleCell research2012

Structural basis for the recognition of Asef by adenomatous polyposis coli.

Zhenyi Zhang, Leyi Chen, Lei Gao, Kui Lin, Liang Zhu, Yang Lu, Xiaoshan Shi, Yuan Gao, Jing Zhou, Ping Xu and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

29 citing papers in PubMed, 43 citations in OpenAlex.

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  8. Double inhibition and activation mechanisms of Ephexin family RhoGEFs.Proceedings of the National Academy of Sciences of the United States of America · 2021
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  12. The structural biology of canonical Wnt signalling.Biochemical Society transactions · 2020
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  14. AnFrontiers in genetics · 2020
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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

12 authors at 1 institution in 1 country.

Zhenyi ZhangState Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China.
Leyi Chen
Lei Gao
Kui Lin
Liang Zhu
Yang Lu
Xiaoshan Shi
Yuan Gao
Jing Zhou
Ping Xu
Jian Zhang
Geng Wu
Shanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef), which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains. The APC-activated Asef stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration. In colorectal cancers, truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis. Here, we report crystal structures of the human APC/Asef complex. We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef, conformation of which changes dramatically upon binding to APC. Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays. Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between Asef-DH domain and APC, which possibly leads to a conformational change in Asef that stimulates its GEF activity. Our structures thus elucidate the molecular mechanism of Asef recognition by APC, as well as provide a potential target for pharmaceutical intervention against cancers.

Indexed as

Models, MolecularAdenomatous Polyposis Coli ProteinAmino Acid SequenceBinding SitesComputer SimulationCrystallography, X-RayGuanine Nucleotide Exchange FactorsHumansMolecular Sequence DataMutagenesis, Site-DirectedProtein BindingProtein Structure, TertiaryRecombinant ProteinsRho Guanine Nucleotide Exchange FactorsAdenomatous Polyposis Coli ProteinARHGEF4 protein, humanGuanine Nucleotide Exchange FactorsRecombinant ProteinsRho Guanine Nucleotide Exchange Factors

Identifiers

PMID21788986
PMCPMC3271586
OpenAlexW1993921134

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.