Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
EMBO Rep. 2012 Oct;13(10):930-8. doi: 10.1038/embor.2012.125. Epub 2012 Aug 10.
Isopeptidases are essential regulators of protein ubiquitination and sumoylation. However, only two families of SUMO isopeptidases are at present known. Here, we report an activity-based search with the suicide inhibitor haemagglutinin (HA)-SUMO-vinylmethylester that led to the identification of a surprising new SUMO protease, ubiquitin-specific protease-like 1 (USPL1). Indeed, USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells. C13orf22l--an essential but distant zebrafish homologue of USPL1--also acts on SUMO, indicating functional conservation. We have identified invariant USPL1 residues required for SUMO binding and cleavage. USPL1 is a low-abundance protein that colocalizes with coilin in Cajal bodies. Its depletion does not affect global sumoylation, but causes striking coilin mislocalization and impairs cell proliferation, functions that are not dependent on USPL1 catalytic activity. Thus, USPL1 represents a third type of SUMO protease, with essential functions in Cajal body biology.
异肽酶是蛋白质泛素化和 SUMO 化的重要调节因子。然而，目前只知道两种 SUMO 异肽酶家族。在这里，我们报告了一项基于自杀抑制剂血凝素 (HA)-SUMO-乙烯基甲酯的活性搜索，该搜索导致了一种令人惊讶的新 SUMO 蛋白酶，即泛素特异性蛋白酶样 1 (USPL1) 的鉴定。事实上，USPL1 既不结合也不切割泛素，但在体外和细胞中都是一种有效的 SUMO 异肽酶。C13orf22l--USPL1 的一个必不可少但遥远的斑马鱼同源物--也作用于 SUMO，表明功能保守。我们已经确定了 USPL1 结合和切割 SUMO 所需的不变残基。USPL1 是一种低丰度的蛋白质，与 coilin 在 Cajal 体中共定位。其耗竭不影响全局 SUMO 化，但导致 coilin 明显定位错误，并损害细胞增殖，这些功能不依赖于 USPL1 的催化活性。因此，USPL1 代表了第三种 SUMO 蛋白酶，在 Cajal 体生物学中具有重要功能。
