Abstract
The feed-back auto-regulatory loop between p53 and MDM2 has been extensively investigated. MDM2 is under the transcriptional control of p53, and MDM2 acts as a negative regulator of p53. There is increasing evidence, however, supporting the notion that MDM2 has activities independent of p53. In the absence of p53, MDM2 may retain its role in cell cycle control, differentiation, cell fate determination, DNA repair, transcription regulation, signal transduction of steroid receptors, cellular response to hypoxia, internalization of surface receptors, and other processes. MDM2 also has oncogenic transformational activities independent of p53. Moreover, anti-MDM2 antisense oligonucleotides have in vitro and in vivo antitumor activity and chemosensitizing and radiosensitizing effects in several human cancer models, regardless of their p53 status. In this article, the p53 independent activities of MDM2 and its interactions with various cellular proteins are considered. The studies reviewed provide a basis for developing novel MDM2 inhibitors as a therapy against human malignancies.
Keywords: sarcomas, p53-dependent promoter, nuclear export signal, tumor
Current Cancer Drug Targets
Title: p53-Independent Activities of MDM2 and Their Relevance to Cancer Therapy
Volume: 5 Issue: 1
Author(s): Zhuo Zhang and Ruiwen Zhang
Affiliation:
Keywords: sarcomas, p53-dependent promoter, nuclear export signal, tumor
Abstract: The feed-back auto-regulatory loop between p53 and MDM2 has been extensively investigated. MDM2 is under the transcriptional control of p53, and MDM2 acts as a negative regulator of p53. There is increasing evidence, however, supporting the notion that MDM2 has activities independent of p53. In the absence of p53, MDM2 may retain its role in cell cycle control, differentiation, cell fate determination, DNA repair, transcription regulation, signal transduction of steroid receptors, cellular response to hypoxia, internalization of surface receptors, and other processes. MDM2 also has oncogenic transformational activities independent of p53. Moreover, anti-MDM2 antisense oligonucleotides have in vitro and in vivo antitumor activity and chemosensitizing and radiosensitizing effects in several human cancer models, regardless of their p53 status. In this article, the p53 independent activities of MDM2 and its interactions with various cellular proteins are considered. The studies reviewed provide a basis for developing novel MDM2 inhibitors as a therapy against human malignancies.
Export Options
About this article
Cite this article as:
Zhang Zhuo and Zhang Ruiwen, p53-Independent Activities of MDM2 and Their Relevance to Cancer Therapy, Current Cancer Drug Targets 2005; 5 (1) . https://dx.doi.org/10.2174/1568009053332618
DOI https://dx.doi.org/10.2174/1568009053332618 |
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
-
Structure and Function of HIV-1 Integrase
Current Topics in Medicinal Chemistry Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review
Current Medicinal Chemistry Evaluation of Drug Targeting Strategies and Liposomal Trafficking
Current Pharmaceutical Design Irreversible Inhibition of Serine Proteases – Design and In Vivo Activity of Diaryl α-Aminophosphonate Derivatives
Current Medicinal Chemistry Molecular Mechanisms and Targeted Therapies Including Immunotherapy for Non-Small Cell Lung Cancer
Current Cancer Drug Targets Mast Cells as Targets of Pimecrolimus
Current Pharmaceutical Design Investigating ABCB1-Mediated Drug-Drug Interactions: Considerations for In vitro and In vivo Assay Design
Current Drug Metabolism Nanocarriers Based Anticancer Drugs: Current Scenario and Future Perceptions
Current Drug Targets Patents and the Development on Polymer based Nanomaterial (PAMAM Dendrimer) for Biomedical Applications
Recent Patents on Biomedical Engineering (Discontinued) Microbial Polysaccharides and their Derivatives as Current and Prospective Pharmaceuticals
Current Pharmaceutical Design Disruption of Metabolic Pathways - Perspectives for the Treatment of Cancer
Current Cancer Drug Targets RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy
Current Topics in Medicinal Chemistry The Urokinase Receptor Interactome
Current Pharmaceutical Design Targeting Nodal and Cripto-1: Perspectives Inside Dual Potential Theranostic Cancer Biomarkers
Current Medicinal Chemistry Preclinical and Clinical Studies on the Use of Stem Cells for Bone Repair: A Systematic Review
Current Stem Cell Research & Therapy Laparoscopic Approach for Surgical Staging in Early Endometrial Cancer
Current Women`s Health Reviews Four Major Factors Regulate Phosphatidylinositol 3-kinase Signaling Pathway in Cancers Induced by Infection of Human Papillomaviruses
Current Medicinal Chemistry Targeting ErbB Receptors in High-Grade Glioma
Current Pharmaceutical Design Mesenchymal Stem Cell Therapy for Equine Tendinitis
Recent Patents on Regenerative Medicine Application of Mesenchymal Stem Cells in Melanoma: A Potential Therapeutic Strategy for Delivery of Targeted Agents
Current Medicinal Chemistry