Abstract
Cyclin E is essential for progression through the G1-phase of the cell cycle and initiation of DNA replication by interacting with and activating its catalytic partner, the cyclin dependent kinase 2 (Cdk2). Rb, as well as Cdc6, NPAT, and nucleophosmin, critical components of cell proliferation and DNA replication, respectively, are targets of Cyclin E / Cdk2 phosphorylation. There are a number of putative binding sites for E2F in the cyclin E promoter region, suggesting an E2F-dependent regulation. Skp2 and Fbw7 are novel proteins, responsible for ubiquitin-dependent proteolysis of Cyclin E. The tight regulation of cyclin E expression, both at the transcriptional level and by ubiquitin-mediated proteolysis, indicates that it has a major role in the control of the G1- and S-phase transitions. Cyclin E is also transcriptionally regulated during radiation-induced apoptosis of hematopoietic cells. In addition to its biological roles, deregulated cyclin E expression has an established role in tumorigenesis. Cell cycle regulatory molecules, such as cyclin E, are frequently deregulated in different types of cancers, where overexpressed native or low molecular weight forms of Cyclin E have a significant role in oncogenesis. During apoptosis of hematopoietic cells, caspase-dependent proteolysis of Cyclin E generates a p18-Cyclin E variant. Understanding the role of Cyclin E in apoptosis may provide a novel target, which may be effective in cancer therapy. This review summarizes what is known about the biological role of cyclin E, its deregulation in cancer, and the opportunities it may provide as a target in clinical therapy.
Keywords: Apotosis, phosphorylation, proteolysis, hematopoietic
Current Cancer Drug Targets
Title: A Dual Role of Cyclin E in Cell Proliferation and Apotosis May Provide a Target for Cancer Therapy
Volume: 4 Issue: 1
Author(s): S. Mazumder, E. L. DuPree and A. Almasan
Affiliation:
Keywords: Apotosis, phosphorylation, proteolysis, hematopoietic
Abstract: Cyclin E is essential for progression through the G1-phase of the cell cycle and initiation of DNA replication by interacting with and activating its catalytic partner, the cyclin dependent kinase 2 (Cdk2). Rb, as well as Cdc6, NPAT, and nucleophosmin, critical components of cell proliferation and DNA replication, respectively, are targets of Cyclin E / Cdk2 phosphorylation. There are a number of putative binding sites for E2F in the cyclin E promoter region, suggesting an E2F-dependent regulation. Skp2 and Fbw7 are novel proteins, responsible for ubiquitin-dependent proteolysis of Cyclin E. The tight regulation of cyclin E expression, both at the transcriptional level and by ubiquitin-mediated proteolysis, indicates that it has a major role in the control of the G1- and S-phase transitions. Cyclin E is also transcriptionally regulated during radiation-induced apoptosis of hematopoietic cells. In addition to its biological roles, deregulated cyclin E expression has an established role in tumorigenesis. Cell cycle regulatory molecules, such as cyclin E, are frequently deregulated in different types of cancers, where overexpressed native or low molecular weight forms of Cyclin E have a significant role in oncogenesis. During apoptosis of hematopoietic cells, caspase-dependent proteolysis of Cyclin E generates a p18-Cyclin E variant. Understanding the role of Cyclin E in apoptosis may provide a novel target, which may be effective in cancer therapy. This review summarizes what is known about the biological role of cyclin E, its deregulation in cancer, and the opportunities it may provide as a target in clinical therapy.
Export Options
About this article
Cite this article as:
Mazumder S., DuPree L. E. and Almasan A., A Dual Role of Cyclin E in Cell Proliferation and Apotosis May Provide a Target for Cancer Therapy, Current Cancer Drug Targets 2004; 4 (1) . https://dx.doi.org/10.2174/1568009043481669
DOI https://dx.doi.org/10.2174/1568009043481669 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
rDNA Mediated Bioconjugates: Fusion Proteins and their Intended Use in Medicine
Current Topics in Medicinal Chemistry Editorial: Overview on microRNAs in Cancer Development and Virus Infection
MicroRNA Targeting Hormonal Signaling Pathways in Castration Resistant Prostate Cancer
Recent Patents on Anti-Cancer Drug Discovery Repositioning the Old Fungicide Ciclopirox for New Medical Uses
Current Pharmaceutical Design Advances in Imaging Gene-Directed Enzyme Prodrug Therapy
Current Pharmaceutical Biotechnology Prostaglandin J2 Family and the Cardiovascular System
Current Vascular Pharmacology Histone Methyltransferase Inhibitors: Novel Epigenetic Agents for Cancer Treatment
Current Medicinal Chemistry DNA Methylation in Colon Cancer: Challenges and Opportunities
Epigenetic Diagnosis & Therapy (Discontinued) Anticancer Actions of Omega-3 Fatty Acids - Current State and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Natural Products as Anti-Cancerous Therapeutic Molecules Targeted towards Topoisomerases
Current Protein & Peptide Science PI3K/Akt/JNK/c-Jun Signaling Pathway is a Mediator for Arsenite- Induced Cyclin D1 Expression and Cell Growth in Human Bronchial Epithelial Cells
Current Cancer Drug Targets The Immunoregulatory Protein Human B7H3 is a Tumor-Associated Antigen that Regulates Tumor Cell Migration and Invasion
Current Cancer Drug Targets Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets
Anti-Cancer Agents in Medicinal Chemistry Optimising the Azeotropic Drying of 18F-Fluorine Wayto Improve the 18F-Fluorocholine Radiochemical Yield
Current Radiopharmaceuticals Gene Therapy in Plastic and Reconstructive Surgery
Current Gene Therapy Lumiflavin Enhances the Effects of Ionising Radiation on Ovarian Cancer Stem-Like Cells by Inhibiting Autophagy
Anti-Cancer Agents in Medicinal Chemistry A Simple High Efficiency Intra-Islet Transduction Protocol Using Lentiviral Vectors
Current Gene Therapy Meta-Analysis of Anticancer Drug Structures - Significance of Their Polar Allylic Moieties
Anti-Cancer Agents in Medicinal Chemistry Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications
Current Drug Targets Thiazolidinediones Anti-Inflammatory and Anti-Atherosclerotic Effects in Type 2 Diabetes Mellitus
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry