USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.
USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.
复制标题
DOI：
10.1073/pnas.2315163120
复制
发表时间：
2023-12
影响因子：
11.1
通讯作者：
Jin Gan;Adán Pinto-Fernández;D. Flierman;J. L. Akkermans;D. O’Brien;Helene Greenwood;H. C. Scott;Günter Fritz;K. Knobeloch;J. Neefjes;Hans van Dam;H. Ovaa;H. Ploegh;Benedikt M. Kessler;P. Geurink;A. Sapmaz
中科院分区：
文献类型：
--
作者：
Jin Gan;Adán Pinto-Fernández;D. Flierman;J. L. Akkermans;D. O’Brien;Helene Greenwood;H. C. Scott;Günter Fritz;K. Knobeloch;J. Neefjes;Hans van Dam;H. Ovaa;H. Ploegh;Benedikt M. Kessler;P. Geurink;A. Sapmaz
在最强的干扰素诱导蛋白质是ISG 15，其结构类似于泛素（Ub）的头-尾二聚体。ISG 15特异性E1、E2和E3型活性催化宿主蛋白的ISG化。这需要通过USP 18将pro-ISG 15预先蛋白水解转化为其成熟形式。USP 18也能够去ISG化。基于活性的蛋白质谱的应用显示，去泛素化酶USP 16同样可以将pro-ISG 15转化为成熟ISG 15以及去ISG化宿主底物。USP 16介导的去ISG化的主要底物包括参与代谢的酶，表明ISG化循环在响应干扰素的代谢控制中可能发挥作用。因此，多个DUB控制暴露于干扰素后的ISGylation水平，如在病毒感染或炎症期间发生的那样。
Significance Among the strongest interferon-induced proteins is ISG15, which structurally resembles a head-to-tail dimer of ubiquitin (Ub). ISG15-specific E1-, E2-, and E3-type activities catalyze ISGylation of host proteins. This requires a prior proteolytic conversion of pro-ISG15 to its mature form by USP18. USP18 is also capable of deISGylation. Application of activity-based protein profiling shows that the deubiquitinase USP16 can likewise convert pro-ISG15 to mature ISG15, as well as deISGylate host substrates. Prominent substrates for USP16-mediated deISGylation include enzymes involved in metabolism, suggesting a possible role for the ISGylation cycle in the control of metabolism in response to interferons. Multiple DUBs thus control the levels of ISGylation upon exposure to interferons, as would occur during virus infection or inflammation.