Ubiquitin signals proteolysis-independent stripping of transcription factors.
Ubiquitin signals proteolysis-independent stripping of transcription factors.
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DOI：
10.1016/j.molcel.2014.02.002
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发表时间：
2014-03-20
期刊：
影响因子：
16
通讯作者：
Yao, Tingting
中科院分区：
文献类型：
--
作者：
Ndoja, Ada;Cohen, Robert E.;Yao, Tingting
据报道，转录激活因子的泛素化通过蛋白水解和非蛋白水解途径调节转录，但泛素（Ub）信号在非蛋白水解过程中的功能尚不清楚。通过在酿酒酵母中使用异源转录激活子LexA-VP16，我们发现激活子的单泛素融合阻止了激活子和DNA之间的稳定相互作用，导致转录抑制，而激活子却没有降解。我们发现AAA+ atp酶Cdc48及其辅助因子是负责从DNA中提取单泛素化激活因子的Ub受体。我们的研究结果表明，激活因子的去泛素化对转录激活至关重要。LexA-VP16的这些发现在酵母和哺乳动物细胞中分别延伸到天然转录激活因子Met4和R-Smads，已知它们是低聚泛素化的。这些结果揭示了一种以前未被发现的转录调控模式，并说明了Ub和Cdc48在基因表达中的作用是独立于蛋白水解的。
Ubiquitination of transcription activators has been reported to regulate transcription via both proteolytic and non-proteolytic routes, yet the function of the ubiquitin (Ub) signal in the non-proteolytic process is poorly understood. By use of the heterologous transcription activator LexA-VP16 in Saccharomyces cerevisiae, we show that mono-ubiquitin fusion of the activator prevents stable interactions between the activator and DNA, leading to transcription inhibition without activator degradation. We identify the AAA+ ATPase Cdc48 and its cofactors as the Ub receptor responsible for extracting the mono-ubiquitinated activator from DNA. Our results suggest that deubiquitination of the activator is critical for transcription activation. These findings with LexA-VP16 extend in both yeast and mammalian cells to native transcription activators Met4 and R-Smads, respectively, that are known to be oligo-ubiquitinated. The results reveal a previously unidentified mode of transcription regulation and illustrate a role for Ub and Cdc48 in gene expression that is independent of proteolysis.
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