ArticleCurrent biology : CB2015
NDR functions as a physiological YAP1 kinase in the intestinal epithelium.
Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- The Hippo signalling pathway and its impact on eye diseases.Journal of cellular and molecular medicine · 2024Pooled it
- NDR kinase SAX-1 controls dendrite branch-specific elimination during neuronal remodeling in C. elegans.The EMBO journal · 2026Article
- Homer condensates orchestrate YAP-Wnt signaling crosstalk downstream of the Crumbs polarity complex.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Species-specific regulation of necroptosis by STK38-dependent RIPK1 phosphorylation.Cell death and differentiation · 2026Article
- SASH1 Inhibits Gastric Cancer Progression by Regulating YAP1-Mediated Metabolic Reprogramming.Applied biochemistry and biotechnology · 2026Article
- Combined Inhibition of HRAS and MEK Induces Tumor Regression and Restores Myogenic Differentiation in HRAS-Mutant Rhabdomyosarcoma.Cancer research · 2026Article
- Temperature-specific regulation of the NDR kinase Orb6 by the MAPK Sty1 to promote heat stress resilience.Journal of cell science · 2026Article
- Regulation of STK38 by autophagy governs YAP1 activity during paligenosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- STK38 Kinase Promotes Cell Migration Induced by Oncogenic Ras via MerTK Activation.International journal of molecular sciences · 2025Article
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship.Molecular diversity · 2025Review
- USP24 promotes hepatocellular carcinoma progression by deubiquitinating and stabilizing YAP1.Cancer cell international · 2025Article
- Screening the human druggable genome identifies ABHD17B as an anti-fibrotic target in hepatic stellate cells.Nature communications · 2025Article
- ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3.Nature communications · 2025Article
- Atypical Hippo signaling network: uncovering novel insights into head and neck cancer biology and advancements in precision intervention.Frontiers in cell and developmental biology · 2025Review
- Article
- Engineered Biomaterials and Model Systems to Study YAP/TAZ in Cancer.ACS biomaterials science & engineering · 2024Review
- The possible correlation between miR-762, Hippo signaling pathway, TWIST1, and SMAD3 in lung cancer and chronic inflammatory diseases.Scientific reports · 2024Article
- Discovery of a small-molecule NDR1 agonist for prostate cancer therapy.Frontiers in pharmacology · 2024Article
- New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer.Cancers · 2023Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPhosphorylation of the transcriptional coactivator YAP1 is a key event in defining Hippo signaling outputs. Previous studies demonstrated that phosphorylation of YAP1 at serine 127 (S127) sequesters YAP1 in the cytoplasm and consequently inhibits YAP1 transcriptional activity. Mammalian tissue-culture experiments suggest that downstream of MST1/2 signaling, LATS1/2 function as YAP1-S127 kinases. However, studies of Mst1/2 knockout mouse models revealed that the identity of the physiological YAP1-S127 kinase(s) in certain tissues, such as the intestine, remains unknown.
resultsWe show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells. By studying NDR1/2-deficient mice, we demonstrate the in vivo relevance of NDR1/2-mediated regulation of YAP1. Specifically, upon loss of NDR1/2 in the intestinal epithelium, endogenous S127 phosphorylation is decreased whereas total YAP1 levels are increased. Significantly, ablation of NDR1/2 from the intestinal epithelium renders mice exquisitely sensitive to chemically induced colon carcinogenesis. Analysis of human colon cancer samples further revealed that NDR2 and YAP1 protein expression are inversely correlated in the majority of samples with high YAP1 expression. Collectively, we report NDR1/2 as physiological YAP1-S127 kinases that might function as tumor suppressors upstream of YAP1 in human colorectal cancer.
conclusionsWe establish mammalian NDR1/2 as bona fide kinases that target YAP1 on S127 in vitro and in vivo. Our findings therefore have important implications for a broad range of research efforts aimed at decoding and eventually manipulating YAP1 biology in cancer settings, regenerative medicine, and possibly also noncancer human diseases.
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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.