ArticleProceedings of the National Academy of Sciences of the United States of America2023
WNK1 controls endosomal trafficking through TRIM27-dependent regulation of actin assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- WNK1 links ionic signals to microtubule dynamics to control pyrin inflammasome assembly.Science advances · 2026Article
- Article
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- Epithelial TRIM27 Inhibits Intestinal Inflammation in Ulcerative Colitis by the USP7/TRIM27-IKK Double Negative-Feedback.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The WNK-OXSR1 osmosensing pathway mediates intestinal regeneration via Hippo-YAP signaling.The EMBO journal · 2026Article
- OTUD4 deubiquitination stabilizes EGFR and activates the PI3K/AKT pathway to promote the invasiveness of triple-negative breast cancer.Cell death & disease · 2026Article
- Knock-down of the long isoform of the WNK1 kinase mitigates the anti-glomerular basement membrane glomerulonephritis in mice.Scientific reports · 2026Article
- Characterization of With-No-Lysine Kinase Family Genes and Roles ofPlants (Basel, Switzerland) · 2025Article
- Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway.Communications biology · 2025Article
- Activation of WNK1 signaling through Piezo1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer.Cancer research · 2025Article
- Biomimetic noncationic lipid nanoparticles for mRNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The protein kinase WNK1 (with-no-lysine 1) influences trafficking of ion and small-molecule transporters and other membrane proteins as well as actin polymerization state. We investigated the possibility that actions of WNK1 on both processes are related. Strikingly, we identified the E3 ligase tripartite motif-containing 27 (TRIM27) as a binding partner for WNK1. TRIM27 is involved in fine tuning the WASH (Wiskott-Aldrich syndrome protein and SCAR homologue) regulatory complex which regulates endosomal actin polymerization. Knockdown of WNK1 reduced the formation of the complex between TRIM27 and its deubiquitinating enzyme USP7 (ubiquitin-specific protease 7), resulting in significantly diminished TRIM27 protein. Loss of WNK1 disrupted WASH ubiquitination and endosomal actin polymerization, which are necessary for endosomal trafficking. Sustained receptor tyrosine kinase (RTK) expression has long been recognized as a key oncogenic signal for the development and growth of human malignancies. Depletion of either WNK1 or TRIM27 significantly increased degradation of the epidermal growth factor receptor (EGFR) following ligand stimulation in breast and lung cancer cells. Like the EGFR, the RTK AXL was also affected similarly by WNK1 depletion but not by inhibition of WNK1 kinase activity. This study uncovers a mechanistic connection between WNK1 and the TRIM27-USP7 axis and extends our fundamental knowledge about the endocytic pathway regulating cell surface receptors.
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