Pelzer Christiane, Kassner Ingrid, Matentzoglu Konstantin, Singh Rajesh K, Wollscheid Hans-Peter, Scheffner Martin, Schmidtke Gunter, Groettrup Marcus
Division of Immunology, Department of Biology, University of Constance, 78457 Konstanz, Germany.
J Biol Chem. 2007 Aug 10;282(32):23010-4. doi: 10.1074/jbc.C700111200. Epub 2007 Jun 19.
UBE1 is known as the human ubiquitin-activating enzyme (E1), which activates ubiquitin in an ATP-dependent manner. Here, we identified a novel human ubiquitin-activating enzyme referred to as UBE1L2, which also shows specificity for ubiquitin. The UBE1L2 sequence displays a 40% identity to UBE1 and also contains an ATP-binding domain and an active site cysteine conserved among E1 family proteins. UBE1L2 forms a covalent link with ubiquitin in vitro and in vivo, which is sensitive to reducing conditions. In an in vitro polyubiquitylation assay, recombinant UBE1L2 could activate ubiquitin and transfer it onto the ubiquitin-conjugating enzyme UbcH5b. Ubiquitin activated by UBE1L2 could be used for ubiquitylation of p53 by MDM2 and supported the autoubiquitylation of the E3 ubiquitin ligases HectH9 and E6-AP. The UBE1L2 mRNA is most abundantly expressed in the testis, suggesting an organ-specific regulation of ubiquitin activation.
UBE1被认为是人类泛素激活酶（E1），它以ATP依赖的方式激活泛素。在此，我们鉴定出一种新型的人类泛素激活酶，称为UBE1L2，它对泛素也具有特异性。UBE1L2序列与UBE1有40%的同一性，并且还包含一个ATP结合结构域和一个在E1家族蛋白中保守的活性位点半胱氨酸。UBE1L2在体外和体内都与泛素形成共价连接，这种连接对还原条件敏感。在体外多聚泛素化试验中，重组UBE1L2可以激活泛素并将其转移到泛素结合酶UbcH5b上。由UBE1L2激活的泛素可用于MDM2介导的p53泛素化，并支持E3泛素连接酶HectH9和E6-AP的自身泛素化。UBE1L2 mRNA在睾丸中表达最为丰富，提示泛素激活存在器官特异性调控。
