丹麦哥本哈根大学Chunaram Choudhary课题组发现，对泛素化占据和周转率进行全局定点分辨分析揭示系统特性。该项研究成果于2024年4月15日在线发表在《细胞》杂志上。

研究人员展示了全局性泛素化位点占据和半衰期的综合情况。泛素化位点占据跨越四个数量级，但泛素化位点占据的中位数比磷酸化位点占据低三个数量级。蛋白酶体抑制剂对泛素化位点的占据、周转率和调控密切相关，这些属性区分了参与蛋白酶体降解和细胞信号传导的位点。与非结构化区域的位点相比，结构化蛋白质区域的位点半衰期更长，蛋白酶体抑制剂的上调作用更强。

重要的是，研究人员发现了一种监控机制，它能快速且不分位点地解除所有泛素特异性E1和E2酶的泛素化，保护它们免受旁观者泛素化的累积。这项工作提供了泛素化特性的系统级定量视图，并揭示了泛素化依赖性管理的通用原理。

据了解，泛素化调节真核细胞中的大多数蛋白质和生物过程。然而，泛素化的特定位点占据（化学计量）和周转率尚未量化。

附：英文原文

Title: Global, site-resolved analysis of ubiquitylation occupancy and turnover rate reveals systems properties

Author: Gabriela Prus, Shankha Satpathy, Brian T. Weinert, Takeo Narita, Chunaram Choudhary

Issue&Volume: 2024-04-15

Abstract: Ubiquitylation regulates most proteins and biological processes in a eukaryotic cell. However, the site-specific occupancy (stoichiometry) and turnover rate of ubiquitylation have not been quantified. Here we present an integrated picture of the global ubiquitylation site occupancy and half-life. Ubiquitylation site occupancy spans over four orders of magnitude, but the median ubiquitylation site occupancy is three orders of magnitude lower than that of phosphorylation. The occupancy, turnover rate, and regulation of sites by proteasome inhibitors are strongly interrelated, and these attributes distinguish sites involved in proteasomal degradation and cellular signaling. Sites in structured protein regions exhibit longer half-lives and stronger upregulation by proteasome inhibitors than sites in unstructured regions. Importantly, we discovered a surveillance mechanism that rapidly and site-indiscriminately deubiquitylates all ubiquitin-specific E1 and E2 enzymes, protecting them against accumulation of bystander ubiquitylation. The work provides a systems-scale, quantitative view of ubiquitylation properties and reveals general principles of ubiquitylation-dependent governance.

DOI: 10.1016/j.cell.2024.03.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00315-5