ArticleProceedings of the National Academy of Sciences of the United States of America2018
PI5P4Kγ functions in DTX1-mediated Notch signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- PBMC-derived RNA signatures show impaired ability to regulate immune responses in women developing preeclampsia†.Biology of reproduction · 2026Article
- The expanding landscape of Deltex: signaling crosstalk and clinical implications.Cellular and molecular life sciences : CMLS · 2026Review
- Subtype-Independent Dysregulation of the Notch Signaling Pathway and Its miRNA Regulators in Breast Cancer.Biomedicines · 2025Article
- DTX1 Modulates Microglial M1 Polarization and Exacerbates Neuroinflammation in Traumatic Brain Injury Model Rats through NF-κB/IRF5.Molecular neurobiology · 2025Article
- Application of chemical similarity and bioisosteres to find allosteric inhibitors of type 2 lipid kinase γ.Scientific reports · 2025Article
- PI5P4K inhibitors: promising opportunities and challenges.The FEBS journal · 2025Review
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Gambogic acid inhibits HBx-mediated hepatitis B virus replication by targeting the DTX1-Notch signaling pathway.Virus research · 2024Article
- The DTX Protein Family:Cells · 2023Review
- Development of potent and selective degraders of PI5P4Kγ.European journal of medicinal chemistry · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
- Small molecules targeting endocytic uptake and recycling pathways.Frontiers in cell and developmental biology · 2023Review
- Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.Frontiers in cell and developmental biology · 2023Article
- Notch Signaling Promotes Mature T-Cell Lymphomagenesis.Cancer research · 2022Article
- Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode.Journal of medicinal chemistry · 2022Article
- E3 Ubiquitin Ligase Regulators of Notch Receptor Endocytosis: From Flies to Humans.Biomolecules · 2022Review
- Article
- Spatial regulation and generation of diversity in signaling pathways.Journal of biosciences · 2021Review
- Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Notch signaling is an evolutionarily conserved pathway that is essential for development, where it controls processes ranging from cell differentiation to survival. Transport through endosomes is a critical step in regulating Notch signaling capacity, where the E3 ubiquitin ligase DTX1 is thought to control Notch1 intracellular transport decisions by direct receptor ubiquitination. However, how DTX1 regulates Notch1 transport within endosomes and the consequence of Notch1 ubiquitination by DTX1 remain unresolved. Here we demonstrate that DTX1 colocalizes with Notch1 on tubulovesicular recycling endosomes. We find that DTX1 silencing leads to enhanced Notch1 recycling from this compartment to the cell surface via a rab4a-mediated transport route. This, in turn, increases Notch1 cell-surface levels and enhances signaling. Surprisingly, we discovered that DTX1 depletion also elevates Notch1 activity mediated by a mutant form of the receptor that lacks lysine residues for ubiquitination, suggesting that DTX1 targets additional factors. Using an activity-based screen for ubiquitination targets, we identified multiple DTX1 substrates including PI5P4Kγ, a lipid kinase involved in PI(4,5)P
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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.