Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Oncol Rep. 2012 Nov;28(5):1924-8. doi: 10.3892/or.2012.2005. Epub 2012 Aug 31.
Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein that promotes p53 activation in several cancer cell lines, including MCF7, U2OS and A549 cells. In this study, we demonstrated that TRIAD1 is a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). TRIAD1 was found to interact with and be ubiquitinated by MDM2. RNA interference against MDM2 increased endogenous TRIAD1 protein stability. The functional study results suggested that TRIAD1 degradation by MDM2 suppresses TRIAD1-mediated cell growth. These data suggested a novel negative regulatory mechanism of TRIAD1 via MDM2 E3 ligase ubiquitination.
两个环指和 DRIL1（TRIAD1）是一种促凋亡蛋白，可在包括 MCF7、U2OS 和 A549 细胞在内的几种癌细胞系中促进 p53 的激活。在这项研究中，我们证明了 TRIAD1 是一种新型的泛素化靶标，可通过鼠双微体 2（MDM2）进行蛋白酶体依赖性降解。发现 TRIAD1 与 MDM2 相互作用并被其泛素化。针对 MDM2 的 RNA 干扰增加了内源性 TRIAD1 蛋白的稳定性。功能研究结果表明，MDM2 介导的 TRIAD1 降解抑制了 TRIAD1 介导的细胞生长。这些数据表明通过 MDM2 E3 连接酶泛素化对 TRIAD1 进行了一种新的负调控机制。
