Department of Biology II, Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
J Cell Biochem. 2011 Feb;112(2):439-44. doi: 10.1002/jcb.22998.
In mammals Dnmt1 is the DNA methyltransferase chiefly responsible for maintaining genomic methylation patterns through DNA replication cycles, but how its maintenance activity is controlled is still not well understood. Interestingly, Uhrf1, a crucial cofactor for maintenance of DNA methylation by Dnmt1, is endowed with E3 ubiquitin ligase activity. Here, we show that both Dnmt1 and Uhrf1 coprecipitate with ubiquitin specific peptidase 7 (Usp7), a de-ubiquitinating enzyme. Overexpression of Uhrf1 and Usp7 resulted in opposite changes in the ubiquitination status and stability of Dnmt1. Our findings suggest that, by balancing Dnmt1 ubiquitination, Usp7 and Uhrf1 fine tune Dnmt1 stability.
在哺乳动物中，Dnmt1 是主要的 DNA 甲基转移酶，负责通过 DNA 复制周期维持基因组甲基化模式，但 Dnmt1 的维持活性如何受到控制仍不清楚。有趣的是，Uhrf1 是 Dnmt1 维持 DNA 甲基化的关键辅助因子，具有 E3 泛素连接酶活性。在这里，我们表明 Dnmt1 和 Uhrf1 都与泛素特异性肽酶 7（Usp7）共沉淀，Usp7 是一种去泛素化酶。Uhrf1 和 Usp7 的过表达导致 Dnmt1 的泛素化状态和稳定性发生相反的变化。我们的发现表明，通过平衡 Dnmt1 的泛素化，Usp7 和 Uhrf1 可以精细调节 Dnmt1 的稳定性。
