Department of Molecular Biology, The Scripps Research Institute, La, Jolla, CA 92037, USA.
J Biol Chem. 2012 Aug 24;287(35):29610-9. doi: 10.1074/jbc.M112.379768. Epub 2012 Jun 22.
Protein modification by SUMO and ubiquitin critically impacts genome stability via effectors that "read" their signals using SUMO interaction motifs or ubiquitin binding domains, respectively. A novel mixed SUMO and ubiquitin signal is generated by the SUMO-targeted ubiquitin ligase (STUbL), which ubiquitylates SUMO conjugates. Herein, we determine that the "ubiquitin-selective" segregase Cdc48-Ufd1-Npl4 also binds SUMO via a SUMO interaction motif in Ufd1 and can thus act as a selective receptor for STUbL targets. Indeed, we define key cooperative DNA repair functions for Cdc48-Ufd1-Npl4 and STUbL, thereby revealing a new signaling mechanism involving dual recruitment by SUMO and ubiquitin for Cdc48-Ufd1-Npl4 functions in maintaining genome stability.
蛋白质的 SUMO 和泛素修饰通过效应物对其信号进行“读取”，分别利用 SUMO 相互作用基序或泛素结合结构域。SUMO 靶向泛素连接酶（STUbL）产生一种新型的 SUMO 和泛素混合信号，该酶使 SUMO 缀合物泛素化。本文中，我们确定“泛素选择性”分拣酶 Cdc48-Ufd1-Npl4 也通过 Ufd1 中的 SUMO 相互作用基序与 SUMO 结合，因此可以作为 STUbL 靶标的选择性受体。事实上，我们定义了 Cdc48-Ufd1-Npl4 和 STUbL 的关键协同 DNA 修复功能，从而揭示了一种新的信号机制，涉及 SUMO 和泛素对 Cdc48-Ufd1-Npl4 功能的双重招募，以维持基因组稳定性。
