Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25
Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25
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DOI：
10.1016/j.molcel.2008.03.021
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发表时间：
2008-06-06
期刊：
影响因子：
16
通讯作者：
Melchior, Frauke
中科院分区：
文献类型：
--
作者：
Meulmeester, Erik;Kunze, Marion;Melchior, Frauke
脊椎动物表达两个不同的 SUMO 蛋白家族（SUMO1 和 SUMO2/3），它们作为翻译后修饰剂发挥不同的功能。许多蛋白质都经过 SUMO1 或 SUMO2/3 特异性修饰，但旁系同源选择性的机制却知之甚少。在筛选 SUMO2/3 结合蛋白时，我们鉴定出了泛素特异性蛋白酶 25 (USP25)。事实证明，USP25 也是 SUMO 化的目标，SUMO2/3 的效率更高。苏酰化发生在 USP25 的两个泛素相互作用基序 (UIM) 内，这是有效水解泛素链所必需的。 USP25 苏酰化会损害泛素链的结合和水解。 SUMO2/3 特异性结合和苏酰化都依赖于 SUMO 相互作用基序 (SIM/SBM)。 USP25 SIM 中的七个氨基酸足以进行 SUMO2/3 特异性结合和缀合，即使脱离结构背景也是如此。因此，旁系同源特异性苏酰化的一种机制可能涉及SIM依赖性地将带硫酯的SUMO1或SUMO2/3 Ubc9招募到靶标上。
Vertebrates express two distinct families of SUMO proteins (SUMO1 and SUMO2/3) that serve distinct functions as posttranslational modifiers. Many proteins are modified specifically with SUMO1 or SUMO2/3, but the mechanisms for paralog selectivity are poorly understood. In a screen for SUMO2/3 binding proteins, we identified Ubiquitin Specific Protease 25 (USP25). USP25 turned out to also be a target for sumoylation, being more efficient with SUMO2/3. Sumoylation takes place within USP25's two ubiquitin interaction motifs (UIMs) that are required for efficient hydrolysis of ubiquitin chains. USP25 sumoylation impairs binding to and hydrolysis of ubiquitin chains. Both SUMO2/3-specific binding and sumoylation depend on a SUMO interaction motif (SIM/SBM). Seven amino acids in the SIM of USP25 are sufficient for SUMO2/3-specific binding and conjugation, even when taken out of structural context. One mechanism for paralog-specific sumoylation may, thus, involve SIM-dependent recruitment of SUMO1 or SUMO2/3 thioester-charged Ubc9 to targets.