Abstract
Cell proliferation is regulated by the cell cycle, and in order to divide the cell must enter a mitotic state. Prior to mitosis the cell is required to pass through a number of checkpoints, including the critical G1/S restriction point governed by the successive phosphorylation of the retinoblastoma protein, pRb. The various proteins and regulatory factors governing pRb phosphorylation have been a major focus of study in recent years, given the central importance of G1/S transition deregulation in cancer development. This review summarises the molecular biology around the G1/S transition, focussing on the critical roles of the transcription factor family E2F and the cyclin-dependent kinase (CDK) and cyclin families involved in E2F release from pRb. Interestingly, E2F release from pRb is associated with cell proliferation; however, above a certain threshold E2F has the potential to trigger apoptosis. The review focuses on the following topics: (i) how E2F and other substrates bind to pRb at the molecular level; (ii) mechanisms by which pRb function is modulated within the cell; (iii) mechanisms that inhibit or enhance cell proliferation via the pRb/E2F pathway; (iv) how E2F can potentiate apoptotic pathways; and (v) what controls whether E2F mediates cell proliferation or apoptosis. The case for the development of agents that perturb pRb:E2F interactions will be made, as a strategy to further inform the molecular biology around this important target and as a therapeutic strategy against cancer.
Keywords: cell proliferation, checkpoints, phosphorylation, apoptosis, cdks, ef family, transcription factor, transactivation domain, pocket-protein binding, rb gene
Current Cancer Drug Targets
Title: Modulation of pRb/E2F Functions in the Regulation of Cell Cycle and in Cancer
Volume: 5 Issue: 3
Author(s): Lucy L. Seville, Nita Shah, Andrew D. Westwell and Weng C. Chan
Affiliation:
Keywords: cell proliferation, checkpoints, phosphorylation, apoptosis, cdks, ef family, transcription factor, transactivation domain, pocket-protein binding, rb gene
Abstract: Cell proliferation is regulated by the cell cycle, and in order to divide the cell must enter a mitotic state. Prior to mitosis the cell is required to pass through a number of checkpoints, including the critical G1/S restriction point governed by the successive phosphorylation of the retinoblastoma protein, pRb. The various proteins and regulatory factors governing pRb phosphorylation have been a major focus of study in recent years, given the central importance of G1/S transition deregulation in cancer development. This review summarises the molecular biology around the G1/S transition, focussing on the critical roles of the transcription factor family E2F and the cyclin-dependent kinase (CDK) and cyclin families involved in E2F release from pRb. Interestingly, E2F release from pRb is associated with cell proliferation; however, above a certain threshold E2F has the potential to trigger apoptosis. The review focuses on the following topics: (i) how E2F and other substrates bind to pRb at the molecular level; (ii) mechanisms by which pRb function is modulated within the cell; (iii) mechanisms that inhibit or enhance cell proliferation via the pRb/E2F pathway; (iv) how E2F can potentiate apoptotic pathways; and (v) what controls whether E2F mediates cell proliferation or apoptosis. The case for the development of agents that perturb pRb:E2F interactions will be made, as a strategy to further inform the molecular biology around this important target and as a therapeutic strategy against cancer.
Export Options
About this article
Cite this article as:
Seville L. Lucy, Shah Nita, Westwell D. Andrew and Chan C. Weng, Modulation of pRb/E2F Functions in the Regulation of Cell Cycle and in Cancer, Current Cancer Drug Targets 2005; 5 (3) . https://dx.doi.org/10.2174/1568009053765816
DOI https://dx.doi.org/10.2174/1568009053765816 |
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
-
From Dual Peroxisome Proliferator Activated Receptor Agonists to Selective Peroxisome Proliferator Activated Receptor Modulators
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Overview of PCTK3/CDK18: A Cyclin-Dependent Kinase Involved in Specific Functions in Post-Mitotic Cells
Current Medicinal Chemistry Biomarkers and Osteosarcoma and IGF
Recent Patents on Biomarkers Enediyne Anticancer Antibiotic Lidamycin: Chemistry, Biology and Pharmacology
Anti-Cancer Agents in Medicinal Chemistry Retinal Ganglion Cell Gene Therapy and Visual System Repair
Current Gene Therapy Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer
Current Genomics Emergence of Functionalized Nanomedicines in Cancer Chemotherapy: Recent Advancements, Current Challenges and Toxicity Considerations
Recent Patents on Nanomedicine Integrins: Regulators of Tissue Function and Cancer Progression
Current Pharmaceutical Design CYP24A1 as a Potential Target for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy
Current Drug Targets N6-Isopentenyladenosine and its Analogue N6-Benzyladenosine Induce Cell Cycle Arrest and Apoptosis in Bladder Carcinoma T24 Cells
Anti-Cancer Agents in Medicinal Chemistry Targeting Chk2 Kinase: Molecular Interaction Maps and Therapeutic Rationale
Current Pharmaceutical Design Drug Discovery Using Yeast as a Model System: A Functional Genomic and Proteomic View
Current Proteomics Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Targeting MAPK Signalling: Prometheus Fire or Pandoras Box?
Current Pharmaceutical Design Is Type 2 Diabetes Mellitus a Predisposal Cause for Developing Hepatocellular Carcinoma?
Current Diabetes Reviews Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets MicroRNAs and Pancreatic Cancer: Current Research and Future Outlooks
Current Signal Transduction Therapy Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Selective Cytotoxic Effects of 5-Trifluoromethoxy-<i>1H</i>-indole-2,3-dione 3-Thiosemicarbazone Derivatives on Lymphoid-originated Cells
Anti-Cancer Agents in Medicinal Chemistry