Sun Sylvia Yao, Crago Aimee
Sarcoma Biology Laboratory, Department of Surgery, Memorial Sloan Kettering Cancer Center, 417 E 618 St, New York, NY 10065, USA.
Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
J Clin Med. 2023 May 24;12(11):3638. doi: 10.3390/jcm12113638.
Murine double minute 2 (MDM2, gene name ) is an oncogene that mainly codes for a protein that acts as an E3 ubiquitin ligase, which targets the tumor suppressor protein p53 for degradation. Overexpression of MDM2 regulates the p53 protein levels by binding to it and promoting its degradation by the 26S proteasome. This leads to the inhibition of p53's ability to regulate cell cycle progression and apoptosis, allowing for uncontrolled cell growth, and can contribute to the development of soft-tissue tumors. The application of cellular stress leads to changes in the binding of MDM2 to p53, which prevents MDM2 from degrading p53. This results in an increase in p53 levels, which triggers either cell cycle arrest or apoptosis. Inhibiting the function of MDM2 has been identified as a potential therapeutic strategy for treating these types of tumors. By blocking the activity of MDM2, p53 function can be restored, potentially leading to tumor cell death and inhibiting the growth of tumors. However, further research is needed to fully understand the implications of MDM2 inhibition for the treatment of soft-tissue tumors and to determine the safety and efficacy of these therapies in clinical trials. An overview of key milestones and potential uses of MDM2 research is presented in this review.
小鼠双微体2（MDM2，基因名称）是一种癌基因，主要编码一种作为E3泛素连接酶的蛋白质，该酶靶向肿瘤抑制蛋白p53进行降解。MDM2的过表达通过与p53结合并促进其被26S蛋白酶体降解来调节p53蛋白水平。这导致p53调节细胞周期进程和凋亡的能力受到抑制，从而允许细胞不受控制地生长，并可能导致软组织肿瘤的发生。细胞应激的应用会导致MDM2与p53结合的变化，从而阻止MDM2降解p53。这导致p53水平升高，进而触发细胞周期停滞或凋亡。抑制MDM2的功能已被确定为治疗这类肿瘤的一种潜在治疗策略。通过阻断MDM2的活性，可以恢复p53的功能，这可能导致肿瘤细胞死亡并抑制肿瘤生长。然而，需要进一步研究以充分了解抑制MDM2对软组织肿瘤治疗的影响，并确定这些疗法在临床试验中的安全性和有效性。本综述介绍了MDM2研究的关键里程碑和潜在用途概述。
