Abstract
The K-, N-, and HRas small GTPases are key regulators of cell physiology and are frequently mutated in human cancers. Despite intensive research, previous efforts to target hyperactive Ras based on known mechanisms of Ras signaling have been met with little success. Several studies have provided compelling evidence for the existence and biological relevance of Ras dimers, establishing a new mechanism for regulating Ras activity in cells additionally to GTP-loading and membrane localization. Existing data also start to reveal how Ras proteins dimerize on the membrane. We propose a dimer model to describe Ras-mediated effector activation, which contrasts existing models of Ras signaling as a monomer or as a 5-8 membered multimer. We also discuss potential implications of this model in both basic and translational Ras biology.
Keywords: Ras signaling, Ras dimer, membrane clustering, cancer, targeted therapy.
Mini-Reviews in Medicinal Chemistry
Title:Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target
Volume: 16 Issue: 5
Author(s): Mo Chen, Alec Peters, Tao Huang and Xiaolin Nan
Affiliation:
Keywords: Ras signaling, Ras dimer, membrane clustering, cancer, targeted therapy.
Abstract: The K-, N-, and HRas small GTPases are key regulators of cell physiology and are frequently mutated in human cancers. Despite intensive research, previous efforts to target hyperactive Ras based on known mechanisms of Ras signaling have been met with little success. Several studies have provided compelling evidence for the existence and biological relevance of Ras dimers, establishing a new mechanism for regulating Ras activity in cells additionally to GTP-loading and membrane localization. Existing data also start to reveal how Ras proteins dimerize on the membrane. We propose a dimer model to describe Ras-mediated effector activation, which contrasts existing models of Ras signaling as a monomer or as a 5-8 membered multimer. We also discuss potential implications of this model in both basic and translational Ras biology.
Export Options
About this article
Cite this article as:
Chen Mo, Peters Alec, Huang Tao and Nan Xiaolin, Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target, Mini-Reviews in Medicinal Chemistry 2016; 16 (5) . https://dx.doi.org/10.2174/1389557515666151001152212
DOI https://dx.doi.org/10.2174/1389557515666151001152212 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Evaluation of the in vitro Chemosensitivity and Correlation with Clinical Outcomes in Lung Cancer using the ATP-TCA
Anti-Cancer Agents in Medicinal Chemistry Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute Lymphoblastic Leukemia
Current Medicinal Chemistry Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?
Current Cancer Drug Targets Factors Controlling Chromatin Organization and Nucleosome Positioning for Establishment and Maintenance of HIV Latency
Current HIV Research Protein Microarrays: Technological Aspects, Applications and Intellectual Property
Recent Patents on Biotechnology Development Course and an Application Strategy for Induced Pluripotent Stem Cells in Regenerative Medicine
Current Stem Cell Research & Therapy An Overview of Naturally Occurring Histone Deacetylase Inhibitors
Current Topics in Medicinal Chemistry New Strategies in the Discovery of Novel Non-Camptothecin Topoisomerase I Inhibitors
Current Medicinal Chemistry Gene and Stem Cell Therapy in the Treatment of Erectile Dysfunction and Pulmonary Hypertension; Potential Treatments for the Common Problem of Endothelial Dysfunction
Current Gene Therapy Quantitative Ultrasound in Diagnosis of Metabolic Bone Diseases
Current Medical Imaging Seek and Destroy: The Use of Natural Compounds for Targeting the Molecular Roots of Cancer
Current Drug Targets Exploiting Novel Cell Cycle Targets in the Development of Anticancer Agents
Current Cancer Drug Targets Molecular Profiles of Sentinel and Non-Sentinel Lymph Nodes in Breast Cancer Progression and Prognosis
Current Cancer Therapy Reviews Tumour Re-Differentiation Effect of Retinoic Acid: A Novel Therapeutic Approach for Advanced Thyroid Cancer
Current Pharmaceutical Design Lymphatics and Inflammation
Current Medicinal Chemistry Benzimidazole Heterocycle as a Privileged Scaffold in Antiviral Agents
Mini-Reviews in Organic Chemistry Eosinophils in Cancer: Favourable or Unfavourable?
Current Medicinal Chemistry Methotrexate-Induced Pneumonitis: Heterogeneity of Bronchoalveolar Lavage and Differences between Cancer and Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued) Radiolabeled Nanoparticles for Cancer Diagnosis and Therapy
Anti-Cancer Agents in Medicinal Chemistry Does Cyclic Dependent Kinase 5 Play a Significant Role in Determination of Stroke Outcome? Possible Therapeutic Implications
Central Nervous System Agents in Medicinal Chemistry