State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan W. Rd., Haidian District, Beijing 100193, China.
Biochem Biophys Res Commun. 2010 Mar 12;393(3):542-5. doi: 10.1016/j.bbrc.2010.02.051. Epub 2010 Feb 12.
Daxx is a multifunctional protein, regulating a wide range of important functions including apoptosis and transcription. However, the way Daxx is regulated is poorly understood. In our previous studies, we have found that Daxx forms a complex with the E3 ubiquitin ligase Mdm2 and the de-ubiquitinase Hausp. In the present work, we show that Daxx is ubiquitinated by Mdm2 in both in vitro and in vivo systems and Mdm2 reduces Daxx expression upon over-expression. We further demonstrate that Hausp critically controls the cellular level of Daxx most likely by inducing Daxx de-ubiquitination. These results reveal Mdm2 and Hausp as important regulators for Daxx functions by controlling Daxx ubiquitination and stability.
Daxx 是一种多功能蛋白，可调节多种重要功能，包括细胞凋亡和转录。然而，Daxx 的调节方式还不太清楚。在我们之前的研究中，我们发现 Daxx 与 E3 泛素连接酶 Mdm2 和去泛素化酶 Hausp 形成复合物。在本工作中，我们证明 Daxx 可在体外和体内系统中被 Mdm2 泛素化，并且 Mdm2 过表达时会降低 Daxx 的表达。我们进一步证明，Hausp 通过诱导 Daxx 去泛素化，显著控制 Daxx 的细胞水平，这表明 Hausp 极有可能是通过诱导 Daxx 去泛素化来控制 Daxx 的细胞水平。这些结果表明 Mdm2 和 Hausp 通过控制 Daxx 的泛素化和稳定性，成为 Daxx 功能的重要调节因子。
