Daxx is reciprocally regulated by Mdm2 and Hausp

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.