Abstract
Ras proteins regulate diverse cellular pathways that are important in the growth and spread of malignancies, including cell proliferation, cell cycle regulation, cell survival, angiogenesis and cell migration. These proteins lack the conventional transmembrane or hydrophobic domain typical of membrane associated proteins. Being small and hydrophilic in nature, these proteins undergo four-stage post-translational lipid modifications viz. prenylation, AAX proteolysis, carboxymethylation and palmitoylation for membrane localization which is important for their function. Therefore, enzymes involved in these modifications viz. farnesyl transferase (FTase), geranylgeranyl transferase-I (GGTase-I), geranylgeranyl transferase-II (GGTase-II), Ras converting enzyme-1 (Rce-1) and isoprenyl cysteine methyl transferase (ICMT) are emerging as potential therapeutic targets for the discovery of newer anticancer therapeutics. Several natural products have shown modulation of these post-translational enzymes. In the present review, natural products isolated from terrestrial as well as marine sources showing ability to modulate these k-Ras post-translational targets and their promise as potential anticancer agents have been discussed. A total of 157 natural products with 141 corresponding references have been covered.
Keywords: k-Ras, cancer, natural products, farnesyl transferase, isoprenyl cysteine methyl transferase
Current Medicinal Chemistry
Title:Modulation of k-Ras Signaling by Natural Products
Volume: 19 Issue: 14
Author(s): S.B. Bharate, B. Singh, R.A. Vishwakarma
Affiliation:
Keywords: k-Ras, cancer, natural products, farnesyl transferase, isoprenyl cysteine methyl transferase
Abstract: Ras proteins regulate diverse cellular pathways that are important in the growth and spread of malignancies, including cell proliferation, cell cycle regulation, cell survival, angiogenesis and cell migration. These proteins lack the conventional transmembrane or hydrophobic domain typical of membrane associated proteins. Being small and hydrophilic in nature, these proteins undergo four-stage post-translational lipid modifications viz. prenylation, AAX proteolysis, carboxymethylation and palmitoylation for membrane localization which is important for their function. Therefore, enzymes involved in these modifications viz. farnesyl transferase (FTase), geranylgeranyl transferase-I (GGTase-I), geranylgeranyl transferase-II (GGTase-II), Ras converting enzyme-1 (Rce-1) and isoprenyl cysteine methyl transferase (ICMT) are emerging as potential therapeutic targets for the discovery of newer anticancer therapeutics. Several natural products have shown modulation of these post-translational enzymes. In the present review, natural products isolated from terrestrial as well as marine sources showing ability to modulate these k-Ras post-translational targets and their promise as potential anticancer agents have been discussed. A total of 157 natural products with 141 corresponding references have been covered.
Export Options
About this article
Cite this article as:
S.B. Bharate, B. Singh, R.A. Vishwakarma , Modulation of k-Ras Signaling by Natural Products, Current Medicinal Chemistry 2012; 19 (14) . https://dx.doi.org/10.2174/092986712800229050
DOI https://dx.doi.org/10.2174/092986712800229050 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
- Announcements
Related Articles
-
New Heterocyclic Compounds: Synthesis, Antioxidant Activity and Computational Insights of Nano-Antioxidant as Ascorbate Peroxidase Inhibitor by Various Cyclodextrins as Drug Delivery Systems
Current Drug Delivery Clinical Management of Arrhythmogenic Right Ventricular Cardiomyopathy: An Update
Current Pharmaceutical Design Sirtuins Family- Recent Development as a Drug Target for Aging, Metabolism, and Age Related Diseases
Current Drug Targets Role of Sulfur Containing Amino Acids as an Adjuvant Therapy in the Prevention of Diabetes and its Associated Complications
Current Diabetes Reviews Curcumin, Hesperidin, and Rutin Selectively Interfere with Apoptosis Signaling and Attenuate Streptozotocin-Induced Oxidative Stress- Mediated Hyperglycemia
Current Neurovascular Research Stem Cell Based Preclinical Drug Development and Toxicity Prediction
Current Pharmaceutical Design Pharmacological Targeting in Inherited Arrhythmia Syndromes
Current Medicinal Chemistry Free Fatty Acids: Circulating Contributors of Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Subject Index To Volume 2
Current Cardiology Reviews Non-glycemic Adverse Effects of Insulin
Current Diabetes Reviews Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target
Current Medicinal Chemistry Mouse Models of Autoimmune Diseases - Autoimmune Myocarditis
Current Pharmaceutical Design Energy Metabolism in the Normal and in the Diabetic Heart
Current Pharmaceutical Design A Review on Novel Ligand Targeted Delivery for Cardiovascular Disorder
Current Drug Delivery Cerebrovascular Complications After Heart Transplantation
Current Cardiology Reviews Controversies About the Chromosomal Stability of Cultivated Mesenchymal Stem Cells: Their Clinical Use is it Safe?
Current Stem Cell Research & Therapy Mitochondrial Physiology and Toxicity (Mitotoxicity); Importance for the Immune System, Programmed Cell Death and Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Daunorubicin Metabolism in Leukemic Cells Isolated from Patients with Acute Myeloid Leukemia
Drug Metabolism Letters Erythropoietin: New Horizon in Cardiovascular Medicine
Recent Patents on Cardiovascular Drug Discovery The Right Ventricle: Biologic Insights and Response to Disease
Current Cardiology Reviews