Abstract
Twelve years ago, the Mdm2 oncogene was shown to bind to and inhibit the tumor suppressor protein, p53. During the past 12 years, both genetic and biochemical studies have demonstrated that Mdm2 is a key negative regulator of the tumor suppressor p53. Mdm2 and p53 form an oscillating auto-regulatory feedback loop, which is tightly controlled to allow the appropriate response to environmental stresses in order to suppress tumor formation. When Mdm2 activity is inappropriately heightened, as it is in many human tumors, p53 activity is attenuated and tumor susceptibility arises. The p53 gene is mutated in 50% of all human tumors, but in those tumors that retain wild type p53, inhibiting Mdm2 activity could activate p53 tumor suppression and therefore provide a therapeutic strategy for the treatment of cancer.
Keywords: the tumor suppressor protein, p53, dna, transcriptional program, cell cycle arrest
Current Cancer Drug Targets
Title: MDM2 is a Central Node in the p53 Pathway: 12 Years and Counting
Volume: 5 Issue: 1
Author(s): Gareth L. Bond, Wenwei Hu and Arnold J. Levine
Affiliation:
Keywords: the tumor suppressor protein, p53, dna, transcriptional program, cell cycle arrest
Abstract: Twelve years ago, the Mdm2 oncogene was shown to bind to and inhibit the tumor suppressor protein, p53. During the past 12 years, both genetic and biochemical studies have demonstrated that Mdm2 is a key negative regulator of the tumor suppressor p53. Mdm2 and p53 form an oscillating auto-regulatory feedback loop, which is tightly controlled to allow the appropriate response to environmental stresses in order to suppress tumor formation. When Mdm2 activity is inappropriately heightened, as it is in many human tumors, p53 activity is attenuated and tumor susceptibility arises. The p53 gene is mutated in 50% of all human tumors, but in those tumors that retain wild type p53, inhibiting Mdm2 activity could activate p53 tumor suppression and therefore provide a therapeutic strategy for the treatment of cancer.
Export Options
About this article
Cite this article as:
Bond L. Gareth, Hu Wenwei and Levine J. Arnold, MDM2 is a Central Node in the p53 Pathway: 12 Years and Counting, Current Cancer Drug Targets 2005; 5 (1) . https://dx.doi.org/10.2174/1568009053332627
DOI https://dx.doi.org/10.2174/1568009053332627 |
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
-
Multitasking of Neuropeptide Y through the Lens of Motifs
Recent Patents on CNS Drug Discovery (Discontinued) Editorial [Special Board Members Issue]
Current Drug Metabolism Preface:
Recent Patents on Nanomedicine Synthesis and Anticancer Properties of Novel Truncated Carbocyclic Nucleoside Analogues
Anti-Cancer Agents in Medicinal Chemistry EDITORIAL (Thematic Issue: Special Thematic Issuue: Development of Biomarkers in Tumors of Digestive System Part I)
Anti-Cancer Agents in Medicinal Chemistry Cetuximab and the Head and Neck Squamous Cell Cancer
Current Topics in Medicinal Chemistry The Role of Neuropeptide Processing Enzymes in Endocrine (Prostate) Cancer: EC 3.4.24.15 (EP24.15)
Protein & Peptide Letters PAI-1 - A Potential Therapeutic Target in Cancer
Current Drug Targets Targeting HIV: Past, Present and Future
Infectious Disorders - Drug Targets Applications of Nuclear Technique to Biological Sciences Labelled Compounds, Radioactive Tracers, and X-Ray Tomography
Current Topics in Medicinal Chemistry Radioimmunotherapy of Cancer Using Monoclonal Antibodies to Target Radiotherapy
Current Pharmaceutical Design Integrative System Biology Strategies for Disease Biomarker Discovery
Combinatorial Chemistry & High Throughput Screening A Review of Pharmacological Treatment Options for Lung Cancer: Emphasis on Novel Nanotherapeutics and Associated Toxicity
Current Drug Targets Outcome Measures Following Sonodynamic Photodynamic Therapy – A Case Series
Current Drug Therapy Nanosuspensions of Poorly Water Soluble Drugs Prepared by Top-down Technologies
Current Pharmaceutical Design Interleukin-15 in Gene Therapy of Cancer
Current Gene Therapy Imatinib Dosing in Gastrointestinal Stromal Tumors (GISTs): When, How Much, and How Long?
Current Clinical Pharmacology Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
Current Neuropharmacology Testosterone Deficiency Syndrome: Cellular and Molecular Mechanism of Action
Current Aging Science Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far
Recent Patents on Anti-Cancer Drug Discovery