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
-
Meet Our Editorial Board Member
Current Signal Transduction Therapy Anti-Invasive and Anti-Metastasis Strategies: New Roads, New Tools and New Hopes
Current Cancer Drug Targets State-of-the-art MR Imaging of Uncommon Hepatocellular Tumours: Fibrolamellar Hepatocellular Carcinoma and Combined Hepatocellularcholangiocarcinoma
Current Medical Imaging Diet After Cholecystectomy
Current Medicinal Chemistry Src Inhibitors and Angiogenesis
Current Pharmaceutical Design CXCR4-targeted Nanoparticles Reduce Cell Viability, Induce Apoptosis and Inhibit SDF-1α Induced BT-549-Luc Cell Migration In Vitro
Current Drug Delivery Phytoestrogens and Mitochondrial Biogenesis in Breast Cancer. Influence of Estrogen Receptors Ratio
Current Pharmaceutical Design Intraepithelial Neoplasia, Dysplasia and Early Cancer of the Digestive Tract: Modifications in Terminology
Current Cancer Therapy Reviews Retraction Notice: The Benefits and Risks of Different Therapies in Preventing Postoperative Nausea and Vomiting in Patients Undergoing Thyroid Surgery
Current Drug Safety Traversing the Skin Barrier with Nano-emulsions
Current Drug Delivery Increased Production of Recombinant O-Phospho-L-Serine Sulfhydrylase from the Hyperthermophilic Archaeon Aeropyrum pernix K1 Using Escherichia coli
Current Biotechnology Paclitaxel Antibody Conjugates and Trehalose for Preserving the Immunulogical Activity After Freeze-Drying
Current Medicinal Chemistry The Effects of Psychological Stress on Depression
Current Neuropharmacology Meet Our Editor:
Reviews on Recent Clinical Trials Meet Our Editorial Board Member
Medicinal Chemistry A Novel Nanocarrier System for Cancer Treatment
Current Nanomedicine Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets
Anti-Cancer Agents in Medicinal Chemistry The Application of Aqueous Two-phase System in the Extraction of Natural Products from Chinese Herbal Medicine: A Review
Current Organic Chemistry Inhibition of Matrix Metalloproteinases (MMPs) as a Potential Strategy to Ameliorate Hypertension-Induced Cardiovascular Alterations
Current Drug Targets Aromatase Inhibitors: A New Reality for the Adjuvant Endocrine Treatment of Early-Stage Breast Cancer in Postmenopausal Women
Mini-Reviews in Medicinal Chemistry