UBE2T是范可尼贫血通路中的E2，并经历负向自我调节。
UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation.
作者信息
Machida Yuichi J, Machida Yuka, Chen Yuefeng, Gurtan Allan M, Kupfer Gary M, D'Andrea Alan D, Dutta Anindya
机构信息
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
出版信息
Mol Cell. 2006 Aug;23(4):589-96. doi: 10.1016/j.molcel.2006.06.024.
The Fanconi anemia pathway is required for the efficient repair of damaged DNA. A key step in this pathway is the monoubiquitination of the FANCD2 protein by the ubiquitin ligase (E3) composed of Fanconi anemia core complex proteins. Here, we show that UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway. UBE2T binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core complex, and is required for the monoubiquitination of FANCD2 in vivo. DNA damage in UBE2T-depleted cells leads to the formation of abnormal chromosomes that are a hallmark of Fanconi anemia. In addition, we show that UBE2T undergoes automonoubiquitination in vivo. This monoubiquitination is stimulated by the presence of the FANCL protein and inactivates UBE2T. Therefore, UBE2T is the E2 in the Fanconi anemia pathway and has a self-inactivation mechanism that could be important for negative regulation of the Fanconi anemia pathway.
范可尼贫血通路对于受损DNA的有效修复是必需的。该通路的关键步骤是由范可尼贫血核心复合蛋白组成的泛素连接酶（E3）对FANCD2蛋白进行单泛素化修饰。在此，我们表明UBE2T是该通路所必需的泛素结合酶（E2）。UBE2T与范可尼贫血核心复合体的泛素连接酶亚基FANCL结合，并且在体内FANCD2的单泛素化修饰过程中是必需的。UBE2T缺失细胞中的DNA损伤会导致异常染色体的形成，这是范可尼贫血的一个标志。此外，我们表明UBE2T在体内会发生自身单泛素化修饰。这种单泛素化修饰受到FANCL蛋白的存在的刺激，并使UBE2T失活。因此，UBE2T是范可尼贫血通路中的E2，并且具有一种自我失活机制，这可能对范可尼贫血通路的负调控很重要。
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