Abstract
Choline kinase (ChoK) is a cytosolic enzyme present in various tissues, whcih catalyzes the phosphorylation of choline to form phosphorylcholine (PCho) in the presence of ATP and magnesium. ChoK is important for the generation of two major membrane phospholipids, phosphatidylcholine (PC) and sphingomyelin (SM) and subsequently for the cell division. ChoK plays a vital role in cell signaling pathways and regulation of cell growth along with PCho involved in malignant transformation through ras oncogenes in different cancers such as breast, lung, colon, prostate, neuroblastoma, hepatic lymphomas, meningiomas and diverse murine tumours. The Ras effectors serine/threonine kinase (Raf-1), the Ral-GDP dissociation stimulator (Ral-GDS) and the phosphatidylinositol 3-kinase (PI3K) are involved in the activation of ChoK during tumorigenesis. ChoK gene induction seems to be associated with certain cell stress or cell defense. Nowadays, RNAi appear to be one of the most promising routes in the cancer therapy. The anticancer potential of both stable expression of siRNAs and their high sequence specificity by RNAi mediated suppression of oncogenic ras in human pancreatic carcinoma, human melanomas and ovarian cancer has been observed. It has an important role in sequence specific post-transcriptional gene silencing mechanism. Presently, the crystal structure of Caenorhabditis elegans choline kinase A-2 (ChoKA-2) is available, which may be useful for comparative modeling of human ChoK and further modeling studies. The present review aims at the general overview of importance, expression, structure, progress in molecular modeling, active site analysis and inhibitors of ChoK. It also highlights the recent role of ChoK in various types of Ras-dependent and Rasindependent carcinogenesis.
Keywords: ChoK, Pcho, Ras GTPases, Ras effectors RNAi, ChoK inhibitors, hemicholinium-3
Current Medicinal Chemistry
Title: Choline Kinase: An Important Target for Cancer
Volume: 13 Issue: 10
Author(s): S. Janardhan, P. Srivani and G. N. Sastry
Affiliation:
Keywords: ChoK, Pcho, Ras GTPases, Ras effectors RNAi, ChoK inhibitors, hemicholinium-3
Abstract: Choline kinase (ChoK) is a cytosolic enzyme present in various tissues, whcih catalyzes the phosphorylation of choline to form phosphorylcholine (PCho) in the presence of ATP and magnesium. ChoK is important for the generation of two major membrane phospholipids, phosphatidylcholine (PC) and sphingomyelin (SM) and subsequently for the cell division. ChoK plays a vital role in cell signaling pathways and regulation of cell growth along with PCho involved in malignant transformation through ras oncogenes in different cancers such as breast, lung, colon, prostate, neuroblastoma, hepatic lymphomas, meningiomas and diverse murine tumours. The Ras effectors serine/threonine kinase (Raf-1), the Ral-GDP dissociation stimulator (Ral-GDS) and the phosphatidylinositol 3-kinase (PI3K) are involved in the activation of ChoK during tumorigenesis. ChoK gene induction seems to be associated with certain cell stress or cell defense. Nowadays, RNAi appear to be one of the most promising routes in the cancer therapy. The anticancer potential of both stable expression of siRNAs and their high sequence specificity by RNAi mediated suppression of oncogenic ras in human pancreatic carcinoma, human melanomas and ovarian cancer has been observed. It has an important role in sequence specific post-transcriptional gene silencing mechanism. Presently, the crystal structure of Caenorhabditis elegans choline kinase A-2 (ChoKA-2) is available, which may be useful for comparative modeling of human ChoK and further modeling studies. The present review aims at the general overview of importance, expression, structure, progress in molecular modeling, active site analysis and inhibitors of ChoK. It also highlights the recent role of ChoK in various types of Ras-dependent and Rasindependent carcinogenesis.
Export Options
About this article
Cite this article as:
Janardhan S., Srivani P. and Sastry N. G., Choline Kinase: An Important Target for Cancer, Current Medicinal Chemistry 2006; 13 (10) . https://dx.doi.org/10.2174/092986706776360923
DOI https://dx.doi.org/10.2174/092986706776360923 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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 Insights on the Antitumoral Properties of Prodiginines
Current Medicinal Chemistry Ascorbic Acid: Its Role in Immune System and Chronic Inflammation Diseases
Mini-Reviews in Medicinal Chemistry Synthesis of Some Coumarinyl Chalcones and their Antiproliferative Activity Against Breast Cancer Cell Lines
Letters in Drug Design & Discovery Possible Use of Autologous Stem Cell Therapies for Alzheimers Disease
Current Alzheimer Research Metabolomics: A Revolution for Novel Cancer Marker Identification
Combinatorial Chemistry & High Throughput Screening Molecular Aspects of Modulation of L-type Calcium Channels by Protein Kinase C
Current Molecular Pharmacology The Role of Mitochondrial Function in Glutamate-Dependent Metabolism in Neuronal Cells
Current Pharmaceutical Design Potential Therapeutic Approaches to Alzheimer’s Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools
Current Neuropharmacology Emerging Roles of P2X Receptors in Cancer
Current Medicinal Chemistry Modulation of GSTP1-1 Oligomerization by Electrophilic Inflammatory Mediators and Reactive Drugs
Inflammation & Allergy - Drug Targets (Discontinued) Targeting SKCa Channels in Cancer: Potential New Therapeutic Approaches
Current Medicinal Chemistry Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery
Current Medicinal Chemistry 5-HT2C Receptor Agonists as Potential Drugs for the Treatment of Obesity
Current Topics in Medicinal Chemistry Modulation of Mitochondrial and Epigenetic Targets by Polyphenols-rich Extract from Araucaria angustifolia in Larynx Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Targeted Radiosensitization in Prostate Cancer
Current Pharmaceutical Design Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions
Recent Patents on Anti-Cancer Drug Discovery Physiological Roles of Neuronal Nicotinic Receptors Subtypes: New Insights on the Nicotinic Modulation of Neurotransmitter Release, Synaptic Transmission and Plasticity
Current Topics in Medicinal Chemistry The Structure and Functions of P-Glycoprotein
Current Medicinal Chemistry Recent Advances in Biological Tissue Imaging with Time-of-Flight Secondary Ion Mass Spectrometry: Polyatomic Ion Sources, Sample Preparation, and Applications
Current Pharmaceutical Design Metallic Colloid Nanotechnology, Applications in Diagnosis and Therapeutics
Current Pharmaceutical Design