ArticleProceedings of the National Academy of Sciences of the United States of America2020
Structure and regulation of human epithelial cell transforming 2 protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Anillin mediates unilateral furrowing during cytokinesis by limiting RhoA binding to its effectors.The Journal of cell biology · 2025Article
- The Role of the Swollen State in Cell Proliferation.The Journal of membrane biology · 2025Review
- Identification of hub genes and pathways in Uterine corpus endometrial carcinoma (UCEC): A comprehensiveBiochemistry and biophysics reports · 2024Article
- The CYK-4 GAP domain regulates cortical targeting of centralspindlin to promote contractile ring assembly and facilitate ring dissolution.bioRxiv : the preprint server for biology · 2024Article
- The post-stroke young adult brain has limited capacity to re-express the gene expression patterns seen during early postnatal brain development.Brain pathology (Zurich, Switzerland) · 2024Article
- New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.Molecular pharmacology · 2024Review
- Article
- The DIAPH3 linker specifies a β-actin network that maintains RhoA and Myosin-II at the cytokinetic furrow.Nature communications · 2024Article
- Structural and dynamic changes in P-Rex1 upon activation by PIPbioRxiv : the preprint server for biology · 2024Article
- Patterning of the cell cortex by Rho GTPases.Nature reviews. Molecular cell biology · 2024Review
- Direct investigation of cell contraction signal networks by light-based perturbation methods.Pflugers Archiv : European journal of physiology · 2023Review
- Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.Cancer cell · 2023Article
- Deficiency of mitochondrial calcium uniporter abrogates iron overload-induced cardiac dysfunction by reducing ferroptosis.Basic research in cardiology · 2023Article
- Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.Biology · 2023Article
- Sex-specific molecular differences in glioblastoma: assessing the clinical significance of genetic variants.Frontiers in oncology · 2023Review
- Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation.eLife · 2022Article
- Membrane compartmentalization of Ect2/Cyk4/Mklp1 and NuMA/dynein regulates cleavage furrow formation.The Journal of cell biology · 2022Article
- Evaluation of the role of KPNA2 mutations in breast cancer prognosis using bioinformatics datasets.BMC cancer · 2022Article
- A versatile cortical pattern-forming circuit based on Rho, F-actin, Ect2, and RGA-3/4.The Journal of cell biology · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial cell transforming 2 (Ect2) protein activates Rho GTPases and controls cytokinesis and many other cellular processes. Dysregulation of Ect2 is associated with various cancers. Here, we report the crystal structure of human Ect2 and complementary mechanistic analyses. The data show the C-terminal PH domain of Ect2 folds back and blocks the canonical RhoA-binding site at the catalytic center of the DH domain, providing a mechanism of Ect2 autoinhibition. Ect2 is activated by binding of GTP-bound RhoA to the PH domain, which suggests an allosteric mechanism of Ect2 activation and a positive-feedback loop reinforcing RhoA signaling. This bimodal RhoA binding of Ect2 is unusual and was confirmed with Förster resonance energy transfer (FRET) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) analyses. Several recurrent cancer-associated mutations map to the catalytic and regulatory interfaces, and dysregulate Ect2 in vitro and in vivo. Together, our findings provide mechanistic insights into Ect2 regulation in normal cells and under disease conditions.
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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.