ArticleMolecular cell2011
FKBP12 binds to acylated H-ras and promotes depalmitoylation.
Article in Molecular cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed, 111 citations in OpenAlex.
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Rac1 palmitoylation is required for cardiac stress adaptation and regulation of protein kinase A signaling.JCI insight · 2025Article
- Rab3gap1 palmitoylation cycling modulates cardiomyocyte exocytosis and atrial natriuretic peptide release.Biophysical journal · 2025Article
- ZDHHC18 promotes renal fibrosis development by regulating HRAS palmitoylation.The Journal of clinical investigation · 2025Article
- Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation.Nature structural & molecular biology · 2024Article
- Refining S-acylation: Structure, regulation, dynamics, and therapeutic implications.The Journal of cell biology · 2023Article
- FK506-binding protein, FKBP12, promotes serine utilization and negatively regulates threonine deaminase in fission yeast.iScience · 2022Article
- Post-translational modification of RAS proteins.Current opinion in structural biology · 2021Review
- Post-translational modification of KRAS: potential targets for cancer therapy.Acta pharmacologica Sinica · 2021Review
- Physiological function of FKBP12, a primary target of rapamycin/FK506: a newly identified role in transcription of ribosomal protein genes in yeast.Current genetics · 2021Review
- Roles of palmitoylation in structural long-term synaptic plasticity.Molecular brain · 2021Review
- RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains.Frontiers in molecular biosciences · 2021Review
- Palmitoylation as a Key Regulator of Ras Localization and Function.Frontiers in molecular biosciences · 2021Review
- Scaffold association factor B (SAFB) is required for expression of prenyltransferases and RAS membrane association.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae.PLoS genetics · 2020Article
- Biology, pathology, and therapeutic targeting of RAS.Advances in cancer research · 2020Review
- Bifunctional Small-Molecule Ligands of K-Ras Induce Its Association with Immunophilin Proteins.Angewandte Chemie (International ed. in English) · 2019Article
- Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting.Seminars in cancer biology · 2019Review
- Synthetic Fluorogenic Peptides Reveal Dynamic Substrate Specificity of Depalmitoylases.Cell chemical biology · 2019Article
- The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function.Frontiers in cellular neuroscience · 2019Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
A cycle of palmitoylation/depalmitoylation of H-Ras mediates bidirectional trafficking between the Golgi apparatus and the plasma membrane, but nothing is known about how this cycle is regulated. We show that the prolyl isomerase (PI) FKBP12 binds to H-Ras in a palmitoylation-dependent fashion and promotes depalmitoylation. A variety of inhibitors of the PI activity of FKBP12, including FK506, rapamycin, and cycloheximide, increase steady-state palmitoylation. FK506 inhibits retrograde trafficking of H-Ras from the plasma membrane to the Golgi in a proline 179-dependent fashion, augments early GTP loading of Ras in response to growth factors, and promotes H-Ras-dependent neurite outgrowth from PC12 cells. These data demonstrate that FKBP12 regulates H-Ras trafficking by promoting depalmitoylation through cis-trans isomerization of a peptidyl-prolyl bond in proximity to the palmitoylated cysteines.
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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.