Tumor Suppression Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, Australia.
Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
J Mol Cell Biol. 2019 Mar 1;11(3):231-244. doi: 10.1093/jmcb/mjz007.
The mouse double minute 4 (MDM4) is emerging from the shadow of its more famous relative MDM2 and is starting to steal the limelight, largely due to its therapeutic possibilities. MDM4 is a vital regulator of the tumor suppressor p53. It restricts p53 transcriptional activity and also, at least in development, facilitates MDM2's E3 ligase activity toward p53. These functions of MDM4 are critical for normal cell function and a proper response to stress. Their importance for proper cell maintenance and proliferation identifies them as a risk for deregulation associated with the uncontrolled growth of cancer. MDM4 tails are vital for its function, where its N-terminus transactivation domain engages p53 and its C-terminus RING domain binds to MDM2. In this review, we highlight recently identified cellular functions of MDM4 and survey emerging therapies directed to correcting its dysregulation in disease.
鼠双微体基因 4（MDM4）正逐渐摆脱其更为知名的“亲戚”MDM2 的阴影，开始崭露头角，这主要归功于其治疗潜力。MDM4 是肿瘤抑制因子 p53 的重要调节因子。它限制了 p53 的转录活性，至少在发育过程中，促进了 MDM2 对 p53 的 E3 连接酶活性。MDM4 的这些功能对于正常细胞功能和对压力的适当反应至关重要。它们对于适当的细胞维持和增殖很重要，这使它们成为与癌症失控生长相关的失调风险因素。MDM4 的尾部对于其功能至关重要，其 N 端转录激活结构域与 p53 结合，其 C 端 RING 结构域与 MDM2 结合。在这篇综述中，我们重点介绍了 MDM4 最近确定的细胞功能，并调查了针对其在疾病中失调的新兴治疗方法。
Zotero 插件
