ArticlePloS one2011
APC(cdh1) mediates degradation of the oncogenic Rho-GEF Ect2 after mitosis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- A novel role of AURKA kinase in erythroblast enucleation.Haematologica · 2024Article
- DNA-PK promotes activation of the survival kinase AKT in response to DNA damage through an mTORC2-ECT2 pathway.Science signaling · 2022Article
- Discovery and Validation of a Compound to Target Ewing's Sarcoma.Pharmaceutics · 2021Article
- A feedforward circuit shaped by ECT2 and USP7 contributes to breast carcinogenesis.Theranostics · 2020Article
- Effect of Ect2 Expression on the Growth of Triple-Negative Breast Cancer Cells with Paclitaxel Intervention.OncoTargets and therapy · 2020Article
- Polymerase-δ-interacting protein 2 activates the RhoGEF epithelial cell transforming sequence 2 in vascular smooth muscle cells.American journal of physiology. Cell physiology · 2019Article
- Cytoplasmic expression of epithelial cell transforming sequence 2 in lung adenocarcinoma and its implications for malignant progression.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Cytokinesis defects and cancer.Nature reviews. Cancer · 2019Review
- Heterogeneity in sarcoma cell lines reveals enhanced motility of tetraploid versus diploid cells.Oncotarget · 2017Article
- Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016Review
- The dynamic behavior of Ect2 in response to DNA damage.Scientific reports · 2016Article
- Controlling the switches: Rho GTPase regulation during animal cell mitosis.Cellular signalling · 2014Review
- Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease.Oncogene · 2014Review
- MgcRacGAP interacts with cingulin and paracingulin to regulate Rac1 activation and development of the tight junction barrier during epithelial junction assembly.Molecular biology of the cell · 2014Article
- Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis.Biochimica et biophysica acta · 2014Review
- Epithelial junctions and Rho family GTPases: the zonular signalosome.Small GTPases · 2014Review
- Rho GTPases as regulators of mitosis and cytokinesis in mammalian cells.Small GTPases · 2014Review
- Spatiotemporal organization of Aurora-B by APC/CCdh1 after mitosis coordinates cell spreading through FHOD1.Journal of cell science · 2013Article
- Article
- Cell cycle regulation of Rho signaling pathways.Cell cycle (Georgetown, Tex.) · 2012Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBesides regulation of actin cytoskeleton-dependent functions, Rho GTPase pathways are essential to cell cycle progression and cell division. Rho, Rac and Cdc42 regulate G1 to S phase progression and are involved in cytokinesis. RhoA GDP/GTP cycling is required for normal cytokinesis and recent reports have shown that the exchange factor Ect2 and the GTPase activating protein MgcRacGAP regulate RhoA activity during mitosis. We previously showed that the transcription factors E2F1 and CUX1 regulate expression of MgcRacGAP and Ect2 as cells enter S-phase. METHODOLOGY/PRINCIPAL
findingsWe now report that Ect2 is subject to proteasomal degradation after mitosis, following ubiquitination by the APC/C complex and its co-activator Cdh1. A proper nuclear localization of Ect2 is necessary for its degradation. APC-Cdh1 assembles K11-linked poly-ubiquitin chains on Ect2, depending upon a stretch of ∼25 amino acid residues that contain a bi-partite NLS, a conventional D-box and two TEK-like boxes. Site-directed mutagenesis of target sequences generated stabilized Ect2 proteins. Furthermore, such degradation-resistant mutants of Ect2 were found to activate RhoA and subsequent signalling pathways and are able to transform NIH3T3 cells. CONCLUSIONS/SIGNIFICANCE: Our results identify Ect2 as a bona fide cell cycle-regulated protein and suggest that its ubiquitination-dependent degradation may play an important role in RhoA regulation at the time of mitosis. Our findings raise the possibility that the overexpression of Ect2 that has been reported in some human tumors might result not only from deregulated transcription, but also from impaired degradation.
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