ArticleOncotarget2015
Destabilisation of dimeric 14-3-3 proteins as a novel approach to anti-cancer therapeutics.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Discovery of Dimer-Dependent Aminoacrylamide Molecular Glues for 14-3-3 Protein-Protein Interactions.ACS medicinal chemistry letters · 2026Article
- Is 14-3-3 the Combination to Unlock New Pathways to Improve Metabolic Homeostasis and β-Cell Function?Diabetes · 2023Review
- Autonomous Synthesis of Functional, Permanently Phosphorylated Proteins for Defining the Interactome of Monomeric 14-3-3ζ.ACS central science · 2023Article
- 14-3-3ζ Constrains insulin secretion by regulating mitochondrial function in pancreatic β cells.JCI insight · 2022Article
- Article
- The Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ.Molecules (Basel, Switzerland) · 2021Article
- Targeting 14-3-3ε activates apoptotic signaling to prevent cutaneous squamous cell carcinoma.Carcinogenesis · 2021Article
- The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases.International journal of molecular sciences · 2020Review
- Review
- Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases.Molecular neurobiology · 2020Review
- Molecular Dynamics Investigations Suggest a Non-specific Recognition Strategy of 14-3-3σ Protein by Tweezer: Implication for the Inhibition Mechanism.Frontiers in chemistry · 2019Article
- Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation.Molecules (Basel, Switzerland) · 2018Article
- Role of salt bridges in the dimer interface of 14-3-3ζ in dimer dynamics, N-terminal α-helical order, and molecular chaperone activity.The Journal of biological chemistry · 2018Article
- The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity.Frontiers in oncology · 2018Review
- Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets.PloS one · 2017Article
- 14-3-3ζ regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function.Nature communications · 2016Article
- Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4: ROLE OF CaMK2D IN THE EPIGENETIC REGULATION OF ID4 GENE EXPRESSION.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
14-3-3 proteins play a pivotal role in controlling cell proliferation and survival, two commonly dysregulated hallmarks of cancers. 14-3-3 protein expression is enhanced in many human cancers and correlates with more aggressive tumors and poor prognosis, suggesting a role for 14-3-3 proteins in tumorigenesis and/or progression. We showed previously that the dimeric state of 14-3-3 proteins is regulated by the lipid sphingosine, a physiological inducer of apoptosis. As the functions of 14-3-3 proteins are dependent on their dimeric state, this sphingosine-mediated 14-3-3 regulation provides a possible means to target dimeric 14-3-3 for therapeutic effect. However, sphingosine mimics are needed that are not susceptible to sphingolipid metabolism. We show here the identification and optimization of sphingosine mimetics that render dimeric 14-3-3 susceptible to phosphorylation at a site buried in the dimer interface and induce mitochondrial-mediated apoptosis. Two such compounds, RB-011 and RB-012, disrupt 14-3-3 dimers at low micromolar concentrations and induce rapid down-regulation of Raf-MAPK and PI3K-Akt signaling in Jurkat cells. Importantly, both RB-011 and RB-012 induce apoptosis of human A549 lung cancer cells and RB-012, through disruption of MAPK signaling, reduces xenograft growth in mice. Thus, these compounds provide proof-of-principle for this novel 14-3-3-targeting approach for anti-cancer drug discovery.
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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.