ArticleThe Journal of biological chemistry2012
DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on induction of neuronal differentiation in cultured cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 147 citations in OpenAlex.
- ZDHHC5: a pivotal palmitoyltransferase orchestrating signaling networks - unraveling mechanisms and therapeutic horizons.Biomarker research · 2026Review
- Metabolic orchestration of NOD1 signaling by AMPK-mediated phosphorylation of ZDHHC5.iScience · 2026Article
- DHHC5 regulates lacteal function and intestinal lipid absorption by maintaining VEGFR2 localization in lipid rafts.Life metabolism · 2025Article
- Mechanisms and functional implications of ZDHHC5 in cellular physiology and disease.Journal of lipid research · 2025Review
- Influence of palmitoylation in axonal transport mechanisms in neurodegenerative diseases.Frontiers in cellular neuroscience · 2025Review
- Stearoylation cycle regulates the cell surface distribution of the PCP protein Vangl2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Design, synthesis and biological activity evaluation of novel covalent S-acylation inhibitors.Molecular diversity · 2024Article
- Mechanisms and functions of protein S-acylation.Nature reviews. Molecular cell biology · 2024Review
- Pulsed Electric Fields Induce STING Palmitoylation and Polymerization Independently of Plasmid DNA Electrotransfer.Pharmaceutics · 2024Article
- Flotillin-1 palmitoylation is essential for its stability and subsequent tumor promoting capabilities.Oncogene · 2024Article
- Constitutive Plasma Membrane Turnover in T-REx293 cells via Ordered Membrane Domain Endocytosis under Mitochondrial Control.bioRxiv : the preprint server for biology · 2024Article
- Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?Molecules (Basel, Switzerland) · 2023Review
- Diverse Roles of Protein Palmitoylation in Cancer Progression, Immunity, Stemness, and Beyond.Cells · 2023Review
- Repositioning Lomitapide to block ZDHHC5-dependant palmitoylation on SSTR5 leads to anti-proliferation effect in preclinical pancreatic cancer models.Cell death discovery · 2023Article
- Quantification of Protein Palmitoylation by Cysteine-SILAC.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Protein palmitoylation in cancer: molecular functions and therapeutic potential.Molecular oncology · 2023Review
- Local and substrate-specific S-palmitoylation determines subcellular localization of Gαo.Nature communications · 2022Article
- Article
- Protein acylation by saturated very long chain fatty acids and endocytosis are involved in necroptosis.Cell chemical biology · 2021Article
- DHHC21 deficiency attenuates renal dysfunction during septic injury.Scientific reports · 2021Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Post-translational palmitoylation of intracellular proteins is mediated by protein palmitoyltransferases belonging to the DHHC family, which share a common catalytic Asp-His-His-Cys (DHHC) motif. Several members have been implicated in neuronal development, neurotransmission, and synaptic plasticity. We previously observed that mice homozygous for a hypomorphic allele of the ZDHHC5 gene are impaired in context-dependent learning and memory. To identify potentially relevant protein substrates of DHHC5, we performed a quantitative proteomic analysis of stable isotope-labeled neuronal stem cell cultures from forebrains of normal and DHHC5-GT (gene-trapped) mice using the bioorthogonal palmitate analog 17-octadecynoic acid. We identified ∼300 17-octadecynoic acid-modified and hydroxylamine-sensitive proteins, of which a subset was decreased in abundance in DHHC5-GT cells. Palmitoylation and oligomerization of one of these proteins (flotillin-2) was abolished in DHHC5-GT neuronal stem cells. In COS-1 cells, overexpression of DHHC5 markedly stimulated the palmitoylation of flotillin-2, strongly suggesting a direct enzyme-substrate relationship. Serendipitously, we found that down-regulation of DHHC5 was triggered within minutes following growth factor withdrawal from normal neural stem cells, a maneuver that is used to induce neural differentiation in culture. The effect was reversible for up to 4 h, and degradation was partially prevented by inhibitors of ubiquitin-mediated proteolysis. These findings suggest that protein palmitoylation can be regulated through changes in DHHC PAT levels in response to differentiation signals.
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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.