Abstract
RAS oncogenes have been identified in about 30% of all human cancers, particularly in 90% of human pancreatic cancers, 50% of colorectal tumors, and 30% of lung cancers. RAS is a central switch for many signal transduction pathways. The RAS proteins undergo three major posttranslational modification steps to become fully functional: prenylation (farnesylation or geranylgeranylation) of the cysteine residue of the CAAX of the RAS C-terminus (C, cysteine, A, aliphatic amino acid; X, Ser, Met, Glu, and Leu), endoproteolysis to remove the AAX amino acid sequence, and methylation of the newly formed prenylated cysteine C-terminus. It is hypothesized that any of these three steps could be an interference point for targeting RAS signaling to block the growth of the mutant RAS-dominant cancer cells. In the last decade, intensive efforts have been directed to target the prenylation of RAS, resulting in many RAS farnesylation inhibitors, which are in the clinical trials with mixed results. On the other hand, both recent chemical genetic and traditional genetic studies demonstrate that targeting two prenylation-dependent modification enzymes, RAS endoprotease and methyltransferase, might be two additional targets in killing mutant RAS-dependent cancer cells. This mini-review discusses the implications of both RAS endoprotease and methyltransferase as anticancer targets and their respective inhibitors as anticancer agents in cancer therapy.
Keywords: RAS, endoprotease, farnesyltransferase, methyltransferase, anticancer target, inhibitor
Current Signal Transduction Therapy
Title: Targeting Prenylated RAS Modifying Enzymes in Cancer Cells
Volume: 1 Issue: 3
Author(s): Yulong L. Chen
Affiliation:
Keywords: RAS, endoprotease, farnesyltransferase, methyltransferase, anticancer target, inhibitor
Abstract: RAS oncogenes have been identified in about 30% of all human cancers, particularly in 90% of human pancreatic cancers, 50% of colorectal tumors, and 30% of lung cancers. RAS is a central switch for many signal transduction pathways. The RAS proteins undergo three major posttranslational modification steps to become fully functional: prenylation (farnesylation or geranylgeranylation) of the cysteine residue of the CAAX of the RAS C-terminus (C, cysteine, A, aliphatic amino acid; X, Ser, Met, Glu, and Leu), endoproteolysis to remove the AAX amino acid sequence, and methylation of the newly formed prenylated cysteine C-terminus. It is hypothesized that any of these three steps could be an interference point for targeting RAS signaling to block the growth of the mutant RAS-dominant cancer cells. In the last decade, intensive efforts have been directed to target the prenylation of RAS, resulting in many RAS farnesylation inhibitors, which are in the clinical trials with mixed results. On the other hand, both recent chemical genetic and traditional genetic studies demonstrate that targeting two prenylation-dependent modification enzymes, RAS endoprotease and methyltransferase, might be two additional targets in killing mutant RAS-dependent cancer cells. This mini-review discusses the implications of both RAS endoprotease and methyltransferase as anticancer targets and their respective inhibitors as anticancer agents in cancer therapy.
Export Options
About this article
Cite this article as:
Chen L. Yulong, Targeting Prenylated RAS Modifying Enzymes in Cancer Cells, Current Signal Transduction Therapy 2006; 1 (3) . https://dx.doi.org/10.2174/157436206778226897
DOI https://dx.doi.org/10.2174/157436206778226897 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
Call for Papers in Thematic Issues
Metabolism in Inflammation-Induced Cancer
We will talk about the primary mechanisms and principles of inflammation-induced cancer based on the most recent research findings and our understanding of the tumor development process, with an emphasis on the crosstalk between metabolism and inflammation-induced cancer. The regulatory mechanisms of T cell subpopulation differentiation, the regulatory function of ...read more
Related Journals

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
A Review on the Role of Nanosensors in Detecting Cellular miRNA Expression in Colorectal Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting STAT3 Enzyme for Cancer Treatment
Mini-Reviews in Medicinal Chemistry Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention
Current Cancer Drug Targets Cancer and the Endogenous “Pineal Clock”: A Means of Early Diagnosis and Successful Treatment as Well as Prevention of Cancers
Current Aging Science The Control of Cell Cycle in Mouse Primordial Germ Cells: Old and New Players
Current Pharmaceutical Design A Closer Look to Polyesters: Properties, Synthesis, Characterization, and Particle Drug Delivery Applications
Nanoscience & Nanotechnology-Asia Application of Metabolomics in Drug Discovery, Development and Theranostics
Current Metabolomics Screening of Potential Plant Compounds as Survivin Inhibitors and its Anti-Cancer Efficacy by Molecular Docking
Current Enzyme Inhibition Design, Synthesis and Bioactivity Evaluation of Novel Chalcone Derivatives Possessing Tryptophan Moiety with Dual Activities of Anti-Cancer and Partially Restoring the Proliferation of Normal Kidney Cells Pre-Treated with Cisplatin
Anti-Cancer Agents in Medicinal Chemistry Deep Tissue Optical and Optoacoustic Molecular Imaging Technologies for Pre-Clinical Research and Drug Discovery
Current Pharmaceutical Biotechnology Targeting Vascular Endothelial Growth Factor Pathway in First-Line Treatment of Metastatic Colorectal Cancer: State-of-the-Art and Future Perspectives in Clinical and Molecular Selection of Patients
Current Cancer Drug Targets Novel Purine Nucleoside Analogues for Hematological Malignancies
Recent Patents on Anti-Cancer Drug Discovery Liposome-Nanogel Structures for Future Pharmaceutical Applications: An Updated Review
Current Pharmaceutical Design D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier
Current Pharmaceutical Design Analysis of Nickel-Binding Peptides in a Human Hepidermoid Cancer Cell Line by Ni-NTA Affinity Chromatography and Mass Spectrometry
Protein & Peptide Letters Gene Therapy Approaches for Neuroprotection and Axonal Regeneration after Spinal Cord and Spinal Root Injury
Current Gene Therapy Genetic and Epigenetic Studies for Determining Molecular Targets of Natural Product Anticancer Agents
Current Cancer Drug Targets Editorial (Hot Topic: Therapeutic Potential of Fetal Mesenchymal Stem Cells)
Current Stem Cell Research & Therapy Animal Models of Carcinogenesis in Inflamed Colorectum: Potential Use in Chemoprevention Study
Current Drug Targets