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.
State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan W. Rd., Haidian District, Beijing 100193, China. jtang@cau.edu.cn
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Tang
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D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7