ArticleScientific reports2019
A new regulatory mechanism for Raf kinase activation, retinoic acid-bound Crabp1.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Article
- CRABP1 Signalosomes in Non-Canonical Actions of Retinoic Acid-Maintaining Health and Preventing Thyroid Dysfunction in Aging.Endocrines · 2025Article
- CRABP1 Signalosomes in Cellular Stress Response and Health Maintenance.Journal of cellular signaling · 2025Article
- CRABP1-complexes in exosome secretion.Cell communication and signaling : CCS · 2024Article
- Hypothalamic GABAergic Neurons Expressing Cellular Retinoic Acid Binding Protein 1 (CRABP1) Are Sensitive to Metabolic Status and Liraglutide in Male Mice.Neuroendocrinology · 2024Article
- Non-canonical retinoid signaling in neural development, regeneration and synaptic function.Frontiers in molecular neuroscience · 2024Review
- Targeting Cellular Retinoic Acid Binding Protein 1 with Retinoic Acid-like Compounds to Mitigate Motor Neuron Degeneration.International journal of molecular sciences · 2023Article
- Molecular basis for cellular retinoic acid-binding protein 1 in modulating CaMKII activation.Frontiers in molecular biosciences · 2023Article
- The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review.International journal of molecular sciences · 2022Review
- Review
- Mechanisms of Feedback Regulation of Vitamin A Metabolism.Nutrients · 2022Review
- Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression.International journal of molecular sciences · 2021Article
- A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder.Cellular signalling · 2021Article
- Regulation of exosome secretion by cellular retinoic acid binding protein 1 contributes to systemic anti-inflammation.Cell communication and signaling : CCS · 2021Article
- Non-Coding RNAs in Retinoic Acid as Differentiation and Disease Drivers.Non-coding RNA · 2021Review
- Structure-functional relationship of cellular retinoic acid-binding proteins I and II interacting with natural and synthetic ligands.Acta crystallographica. Section D, Structural biology · 2021Article
- Retinoids in Cutaneous Squamous Cell Carcinoma.Nutrients · 2021Review
- Maprotiline Suppresses Cholesterol Biosynthesis and Hepatocellular Carcinoma Progression Through Direct Targeting of CRABP1.Frontiers in pharmacology · 2021Article
- Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases.International journal of molecular sciences · 2020Article
- Molecular targets for endogenous glial cell line-derived neurotrophic factor modulation in striatal parvalbumin interneurons.Brain communications · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
The rapidly accelerated fibrosarcoma (Raf) kinase is canonically activated by growth factors that regulate multiple cellular processes. In this kinase cascade Raf activation ultimately results in extracellular regulated kinase 1/2 (Erk1/2) activation, which requires Ras binding to the Ras binding domain (RBD) of Raf. We recently reported that all-trans retinoic acid (atRA) rapidly (within minutes) activates Erk1/2 to modulate cell cycle progression in stem cells, which is mediated by cellular retinoic acid binding protein 1 (Crabp1). But how atRA-bound Crabp1 regulated Erk1/2 activity remained unclear. We now report Raf kinase as the direct target of atRA-Crabp1. Molecularly, Crabp1 acts as a novel atRA-inducible scaffold protein for Raf/Mek/Erk in cells without growth factor stimulation. However, Crabp1 can also compete with Ras for direct interaction with the RBD of Raf, thereby negatively modulating growth factor-stimulated Raf activation, which can be enhanced by atRA binding to Crabp1. NMR heteronuclear single quantum coherence (HSQC) analyses reveal the 6-strand β-sheet face of Crabp1 as its Raf-interaction surface. We identify a new atRA-mimicking and Crabp1-selective compound, C3, that can also elicit such an activity. This study uncovers a new signal crosstalk between endocrine (atRA-Crabp1) and growth factor (Ras-Raf) pathways, providing evidence for atRA-Crabp1 as a novel modulator of cell growth. The study also suggests a new therapeutic strategy by employing Crabp1-selective compounds to dampen growth factor stimulation while circumventing RAR-mediated retinoid toxicity.
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