ArticleNature structural & molecular biology2007
Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression.
Article in Nature structural & molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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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.
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Who cites it
56 citing papers in PubMed, 96 citations in OpenAlex.
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- A RhoGEF activates RacM to selectively promote motility without affecting macropinocytosis in Entamoeba histolytica.Journal of cell science · 2026Article
- Examining the Role of Asef and Epidermal Growth Factor on Cell Migration and Proliferation in Triple Negative Breast Cancer Epithelial Cells.microPublication biology · 2026Article
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- Potentials of N-Acyl Hydrazones Against Colorectal Cancer: A Mini Review.Anti-cancer agents in medicinal chemistry · 2025Review
- Computer-aided molecular design and optimization of potent inhibitors disrupting APC‒Asef interaction.Acta pharmaceutica Sinica. B · 2024Article
- Article
- Rational design of a sensitivity-enhanced tracer for discovering efficient APC-Asef inhibitors.Nature communications · 2022Article
- ARHGEF9 regulates melanoma morphogenesis in environments with diverse geometry and elasticity by promoting filopodial-driven adhesion.iScience · 2022Article
- Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism.Nature structural & molecular biology · 2022Article
- A RAC-GEF network critical for early intestinal tumourigenesis.Nature communications · 2021Article
- Review
- Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy.Frontiers in molecular biosciences · 2021Review
- Neuroligin-2 dependent conformational activation of collybistin reconstituted in supported hybrid membranes.The Journal of biological chemistry · 2020Article
- Branched actin networks are assembled on microtubules by adenomatous polyposis coli for targeted membrane protrusion.The Journal of cell biology · 2020Article
- The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.The Journal of biological chemistry · 2020Article
- Multiplexed GTPase and GEF biosensor imaging enables network connectivity analysis.Nature chemical biology · 2020Article
- Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions.Nature cell biology · 2020Article
- Vav2 lacks CaJournal of cell science · 2020Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Autoinhibition of the Rho guanine nucleotide exchange factor ASEF is relieved by interaction with the APC tumor suppressor. Here we show that binding of the armadillo repeats of APC to a 'core APC-binding' (CAB) motif within ASEF, or truncation of the SH3 domain of ASEF, relieves autoinhibition, allowing the specific activation of CDC42. Structural determination of autoinhibited ASEF reveals that the SH3 domain forms an extensive interface with the catalytic DH and PH domains to obstruct binding and activation of CDC42, and the CAB motif is positioned adjacent to the SH3 domain to facilitate activation by APC. In colorectal cancer cell lines, full-length, but not truncated, APC activates CDC42 in an ASEF-dependent manner to suppress anchorage-independent growth. We therefore propose a model in which ASEF acts as a tumor suppressor when activated by APC and inactivation of ASEF by mutation or APC truncation promotes tumorigenesis.
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Registered trials
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.