ArticleThe Journal of biological chemistry2020
Ubiquitination of the scaffold protein IQGAP1 diminishes its interaction with and activation of the Rho GTPase CDC42.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Molecular scissors for inflamed lungs: targeting ubiquitin-specific peptidases in acute lung injury.Thorax · 2026Article
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- IQGAP1 participates in bone marrow-derived macrophage recruitment and involves in liver inflammation/fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Article
- IQGAP1: cross-disease target via receptor-pathway networks.Frontiers in oncology · 2025Review
- Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.Communications biology · 2024Article
- Article
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion.Cell death & disease · 2023Article
- ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer.Cell death & disease · 2023Article
- Article
- Review
- CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain.International journal of molecular sciences · 2022Article
- Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- Signaling in the crowded cell.Current opinion in structural biology · 2021Review
- Role of IQGAP1 in Carcinogenesis.Cancers · 2021Review
- PI3K Driver Mutations: A Biophysical Membrane-Centric Perspective.Cancer research · 2021Review
- Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a scaffold protein that interacts with numerous binding partners and thereby regulates fundamental biological processes. The functions of IQGAP1 are modulated by several mechanisms, including protein binding, self-association, subcellular localization, and phosphorylation. Proteome-wide screens have indicated that IQGAP1 is ubiquitinated, but the possible effects of this post-translational modification on its function are unknown. Here we characterized and evaluated the function of IQGAP1 ubiquitination. Using MS-based analysis in HEK293 cells, we identified six lysine residues (Lys-556, -1155, -1230, -1465, -1475, and -1528) as ubiquitination sites in IQGAP1. To elucidate the biological consequences of IQGAP1 ubiquitination, we converted each of these lysines to arginine and found that replacing two of these residues, Lys-1155 and Lys-1230, in the GAP-related domain of IQGAP1 (termed IQGAP1 GRD-2K) reduces its ubiquitination. Moreover, IQGAP1 GRD-2K bound a significantly greater proportion of the two Rho GTPases cell division cycle 42 (CDC42) and Rac family small GTPase 1 (RAC1) than did WT IQGAP1. Consistent with this observation, reconstitution of IQGAP1-null cells with IQGAP1 GRD-2K significantly increased the amount of active CDC42 and enhanced cell migration significantly more than WT IQGAP1. Our results reveal that ubiquitination of the CDC42 regulator IQGAP1 alters its ability to bind to and activate this GTPase, leading to physiological effects. Collectively, these findings expand our view of the role of ubiquitination in cell signaling and provide additional insight into CDC42 regulation.
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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.