ArticleBiochimica et biophysica acta2013
A new mechanism of RhoA ubiquitination and degradation: roles of SCF(FBXL19) E3 ligase and Erk2.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 94 citations in OpenAlex.
- Article
- RHOA controls oncogenic B cell receptor signaling in aggressive lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multilayered regulation of cytoskeletal protein abundance: autoregulatory mechanisms of actin and tubulin.Experimental & molecular medicine · 2026Review
- RICH1 enhances pro-inflammatory TAM infiltration in breast cancer via promoting TRIM21-mediated ubiquitination of RhoA and inhibiting STAT3 phosphorylation.NPJ precision oncology · 2025Article
- Neddylation of RhoA impairs its protein degradation and promotes renal interstitial fibrosis progression in diabetic nephropathy.Acta pharmacologica Sinica · 2025Article
- Age-dependent gene expression trajectories during early childhood in children at increased risk for type 1 diabetes.Genes and immunity · 2025Article
- RAB33A promotes metastasis via RhoC accumulation through non-canonical autophagy in cervical cancer.Cell death & disease · 2025Article
- New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.Metabolic brain disease · 2025Review
- FBXL19 in endothelial cells protects the heart from influenza A infection by enhancing antiviral immunity and reducing cellular senescence programs.American journal of physiology. Heart and circulatory physiology · 2024Article
- An Anti-Invasive Role for Mdmx through the RhoA GTPase under the Control of the NEDD8 Pathway.Cells · 2024Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants.Acta dermato-venereologica · 2024Article
- Parkinson's disease risk enhancers in microglia.iScience · 2024Article
- Multi-monoubiquitylation controls VASP-mediated actin dynamics.Journal of cell science · 2024Article
- Article
- Inhibition ofInternational journal of molecular sciences · 2023Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.Oncogenesis · 2023Article
- Smurf1 regulates ameloblast polarization by ubiquitination-mediated degradation of RhoA.Cell proliferation · 2023Article
- Protective role of FBXL19 in Streptococcus pneumoniae-induced lung injury in pneumonia immature mice.Journal of cardiothoracic surgery · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
RhoA is a small GTPase multifunctional protein that regulates cell proliferation and cytoskeletal reorganization. Regulation of its protein stability plays an important role in its biological functions. We have shown that a Skp1-Cul1-F-box (SCF) FBXL19 E3 ubiquitin ligase targets Rac1, a related member of the Rho family for ubiquitination and degradation. Here, SCF(FBXL19) mediates RhoA ubiquitination and proteasomal degradation in lung epithelial cells. Ectopically expressed FBXL19 decreased RhoA wild type, active, and inactive forms. Cellular depletion of FBXL19 increased RhoA protein levels and extended its half-life. FBXL19 bound the small GTPase in the cytoplasm leading to RhoA ubiquitination at Lys(135). A RhoA(K135R) mutant protein was resistant to SCF(FBXL19)-mediated ubiquitination and degradation and exhibited a longer lifespan. Protein kinase Erk2-mediated phosphorylation of RhoA was both sufficient and required for SCF(FBXL19)-mediated RhoA ubiquitination and degradation. Thus, SCF(FBXL19) targets RhoA for its disposal, a process regulated by Erk2. Ectopically expressed FBXL19 reduced phosphorylation of p27 and cell proliferation, a process mediated by RhoA. Further, FBXL19 cellular expression diminished lysophosphatidic acid (LPA)-induced phosphorylation of myosin light chain (MLC) and stress fiber formation. Hence, SCF(FBXL19) functions as a RhoA antagonist during cell proliferation and cytoskeleton rearrangement. These results provide the first evidence of an F-box protein targeting RhoA thereby modulating its cellular lifespan that impacts cell proliferation and cytoskeleton rearrangement.
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