Daxx is reciprocally regulated by Mdm2 and Hausp.

Daxx is reciprocally regulated by Mdm2 and Hausp.
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DOI:
10.1016/j.bbrc.2010.02.051
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发表时间:
2010-03-12
影响因子:
3.1
通讯作者:
Yang, Xiaolu
Yang, Xiaolu
中科院分区:
生物学4区
文献类型:
--
作者:
Tang, Jun;Qu, Like;Pang, Mingsu;Yang, Xiaolu

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Daxx是一种多功能蛋白,调节多种重要功能,包括细胞凋亡和转录。然而,人们对Daxx的监管方式知之甚少。在我们之前的研究中,我们发现Daxx与E3泛素连接酶Mdm2和去泛素酶Hausp形成复合物。在目前的工作中,我们发现Daxx在体内和体外系统都被Mdm2泛素化,并且Mdm2在过表达时降低Daxx的表达。我们进一步证明,Hausp很可能通过诱导Daxx去泛素化来严格控制Daxx的细胞水平。这些结果表明Mdm2和Hausp通过控制Daxx泛素化和稳定性而成为Daxx功能的重要调控因子。
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 deubiquitinase 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 overe-xpression. We further demonstrate that Hausp critically controls the cellular level of Daxx most likely by inducing Daxx deubiquitination. These results reveal Mdm2 and Hausp as important regulators for Daxx functions by controlling Daxx ubiquitination and stability.
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期刊: THERAPEUTIC OLIGONUCLEOTIDES
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