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Considering the Role of Murine Double Minute 2 in the Cardiovascular System?
1Angiogenesis Research Group, School of Kinesiology and Health Sciences, Muscle Health Research Center, Faculty of Health, York University, Toronto, ON, Canada.
Abstract:
The E3 ubiquitin ligase Murine double minute 2 (MDM2) is the main negative regulator of the tumor protein p53 (TP53). Extensive studies over more than two decades have confirmed MDM2 oncogenic role through mechanisms both TP53-dependent and TP53-independent oncogenic function. These studies have contributed to designate MDM2 as a therapeutic target of choice for cancer treatment and the number of patents for MDM2 antagonists has increased immensely over the last years. However, the question of the physiological functions of MDM2 has not been fully resolved yet, particularly when expressed and regulated physiologically in healthy tissue. Cardiovascular complications are almost an inescapable side-effect of anti-cancer therapies. While several MDM2 antagonists are entering phase I, II and even III of clinical trials, this review proposes to bring awareness on the physiological role of MDM2 in the cardiovascular system.
Insights
Murine double minute 2 (MDM2) is a key regulator of tumor protein p53 (TP53) and a cancer therapeutic target. This review highlights MDM2's crucial physiological roles within the cardiovascular system.
Area of Science:
- Oncology
- Cardiovascular Biology
- Molecular Biology
Background:
- Murine double minute 2 (MDM2) is the primary negative regulator of tumor protein p53 (TP53).
- MDM2 exhibits oncogenic functions through both TP53-dependent and independent pathways.
- MDM2 is a validated therapeutic target for cancer, with numerous antagonists in clinical development.
Purpose of the Study:
- To explore the unresolved physiological functions of MDM2 in healthy tissues.
- To raise awareness of MDM2's role in the cardiovascular system.
- To contextualize MDM2's function in light of its known oncogenic roles and therapeutic targeting.
Main Methods:
- This review synthesizes existing literature on MDM2.
- It focuses on studies investigating MDM2's expression and regulation in physiological conditions.
- Emphasis is placed on research examining MDM2's impact on cardiovascular health.
Main Results:
- MDM2 plays a significant role in regulating cellular processes beyond tumor suppression.
- Evidence suggests MDM2 has functions within the cardiovascular system that are not fully understood.
- Cardiovascular complications are a known side effect of anti-cancer therapies targeting MDM2.
Conclusions:
- The physiological functions of MDM2, particularly in the cardiovascular system, require further investigation.
- Understanding MDM2's non-oncogenic roles is crucial for developing safer anti-cancer therapies.
- Further research into MDM2's cardiovascular functions may mitigate treatment-related side effects.
