ArticleProceedings of the National Academy of Sciences of the United States of America2008
Palmitoylation and ubiquitination regulate exit of the Wnt signaling protein LRP6 from the endoplasmic reticulum.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
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Who cites it
93 citing papers in PubMed, 166 citations in OpenAlex.
- Review
- DHHC3-dependent S-Acylation of CRY1 regulates its subcellular localization and repressor function in the circadian clock.bioRxiv : the preprint server for biology · 2026Article
- A Small-Molecule SLD1121 Activates Wnt/β-Catenin Signaling and Promotes Hair Growth via Targeting the Wnt Coreceptor LRP6.JACS Au · 2026Article
- Bridging metabolic reprogramming and targeted therapy: the critical role of S-palmitoylation in cancer.Frontiers in cell and developmental biology · 2026Review
- Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning.bioRxiv : the preprint server for biology · 2025Article
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- Exploring the role of palmitoylation in sepsis: mechanistic insights and future perspectives.Molecular medicine (Cambridge, Mass.) · 2025Review
- The landscape of renal protein S-acylation in mice with lipid-induced nephrotoxicity.Scientific reports · 2025Article
- Palmitoylation regulates myelination by modulating the ZDHHC3-Cadm4 axis in the central nervous system.Signal transduction and targeted therapy · 2024Article
- Mechanisms and functions of protein S-acylation.Nature reviews. Molecular cell biology · 2024Review
- Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia of Drosophila.Journal of cell science · 2024Article
- Flotillin-1 palmitoylation is essential for its stability and subsequent tumor promoting capabilities.Oncogene · 2024Article
- D6PK plasma membrane polarity requires a repeated CXX(X)P motif and PDK1-dependent phosphorylation.Nature plants · 2024Article
- Refining S-acylation: Structure, regulation, dynamics, and therapeutic implications.The Journal of cell biology · 2023Article
- Diverse Roles of Protein Palmitoylation in Cancer Progression, Immunity, Stemness, and Beyond.Cells · 2023Review
- Wnt Signaling Inhibitors and Their Promising Role in Tumor Treatment.International journal of molecular sciences · 2023Review
- Article
- Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth.Science China. Life sciences · 2022Article
- Aberrant Cholesterol Metabolism and Wnt/β-Catenin Signaling Coalesce via Frizzled5 in Supporting Cancer Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Canonical Wnt signaling is initiated by binding of Wnt proteins to members of the Frizzled family and subsequent complex formation with lipoprotein receptor-related proteins 5/6 (LRP5/6). Here, we show that LRP6 is palmitoylated on a juxtamembranous cysteine and that palmitoylation is required for exit from the endoplasmic reticulum (ER). We propose that palmitoylation serves to tilt the long, 23-residue transmembrane domain of LRP6 with respect to the plane of membrane to prevent a hydrophobic mismatch and subsequent recognition by the ER quality control. In support of this model, a palmitoylation-deficient LRP6 mutant could be rescued from ER retention by deletion of two to four residues in the transmembrane domain. Importantly, we found that palmitoylation-deficient LRP6 was retained in the ER by a completely novel monoubiquitination-dependent ER retention mechanism. Mutation of a specific lysine indeed abolished ubiquitination of palmitoylation-deficient LRP6 and led to a rescue from ER retention. Finally, at the cell surface, we found that interplay between palmitoylation and ubiquitination was necessary for efficient Wnt 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.