ArticleJournal of cell science2015
Rac1 augments Wnt signaling by stimulating β-catenin-lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import.
Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Molecular determinants of cholesterol binding to BK channel-forming slo1 subunits.Archives of biochemistry and biophysics · 2026Article
- Non-Canonical MaternalBiology · 2026Article
- A novel tRF-Gly is associated with obesity development through post-transcriptional regulation of lipid metabolism.Cellular & molecular biology letters · 2025Article
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- Interactions between genistein and Wnt pathway in colon adenocarcinoma and early embryos.Heliyon · 2024Article
- Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.Journal of cellular and molecular medicine · 2024Article
- Review
- Endothelial β-catenin upregulation and Y142 phosphorylation drive diabetic angiogenesis via upregulating KDR/HDAC9.Cell communication and signaling : CCS · 2024Article
- The Wnt-pathway corepressor TLE3 interacts with the histone methyltransferase KMT1A to inhibit differentiation in Rhabdomyosarcoma.Oncogene · 2024Article
- The PMA phorbol ester tumor promoter increases canonical Wnt signaling via macropinocytosis.eLife · 2023Article
- Wnt3a-Loaded Extracellular Vesicles Promote Alveolar Epithelial Regeneration after Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.Breast cancer research : BCR · 2022Article
- PI3Kβ-regulated β-catenin mediates EZH2 removal from promoters controlling primed human ESC stemness and primitive streak gene expression.Stem cell reports · 2022Article
- Diallyl disulfide inhibits proliferation, epithelial-mesenchymal transition, and invasion through RORα-mediated downregulation of Wnt1/β-catenin pathway in gastric cancer cells.Journal of food and drug analysis · 2022Article
- The functional roles of the circRNA/Wnt axis in cancer.Molecular cancer · 2022Review
- EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation.Cell death & disease · 2022Article
- Mechanisms of mutant β-catenin in endometrial cancer progression.Frontiers in oncology · 2022Review
- Statin Treatment as a Targeted Therapy for APC-Mutated Colorectal Cancer.Frontiers in oncology · 2022Article
- Loss of Zic3 impairs planar cell polarity leading to abnormal left-right signaling, heart defects and neural tube defects.Human molecular genetics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1-β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin-lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin-LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling.
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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.