Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner.
Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner.
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DOI：
10.1126/science.abf6548
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发表时间：
2021-06-25
期刊：
影响因子：
--
通讯作者：
Taylor JP
中科院分区：
文献类型：
--
作者：
Gwon Y;Maxwell BA;Kolaitis RM;Zhang P;Kim HJ;Taylor JP
应激颗粒是由RNA和蛋白质组成的动态、可逆的缩合物，其在真核细胞中响应于各种应激物而组装，并且在应激去除后通常分解。应力颗粒的组成和组装是很好的理解，但很少有人知道的机制，管理拆卸。受损的拆卸已牵连在一些疾病，包括肌萎缩侧索硬化症，额颞叶痴呆症，和多系统蛋白质病。使用培养的人类细胞，我们发现应激颗粒解体是上下文依赖的：特别是在热休克的设置中，解体需要G3 BP 1的泛素化，G3 BP 1是应激颗粒RNA-蛋白质网络中的中心蛋白。我们发现泛素化的G3 BP 1与内质网相关蛋白FAF 2相互作用，FAF 2参与泛素依赖性分离酶p97/VCP（含valosin-containing蛋白）。因此，靶向G3 BP 1削弱了应激颗粒特异性相互作用网络，导致颗粒解体。G3 BP 1的泛素化介导热诱导应激颗粒的FAF 2和p97/VCP依赖性解体
Stress granules are dynamic, reversible condensates composed of RNA and protein that assemble in eukaryotic cells in response to a variety of stressors and are normally disassembled after stress is removed. The composition and assembly of stress granules is well understood, but little is known about the mechanisms that govern disassembly. Impaired disassembly has been implicated in some diseases including amyotrophic lateral sclerosis, frontotemporal dementia, and multisystem proteinopathy. Using cultured human cells, we found that stress granule disassembly was context-dependent: Specifically in the setting of heat shock, disassembly required ubiquitination of G3BP1, the central protein within the stress granule RNA-protein network. We found that ubiquitinated G3BP1 interacted with the endoplasmic reticulum– associated protein FAF2, which engaged the ubiquitin-dependent segregase p97/VCP (valosin-containing protein). Thus, targeting of G3BP1 weakened the stress granule–specific interaction network, resulting in granule disassembly. Ubiquitination of G3BP1 mediates FAF2- and p97/VCP-dependent disassembly of heat-induced stress granules
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DOI：
10.1073/pnas.0805371105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Mueller, Britta;Klemm, Elizabeth J.;Ploegh, Hidde L.
通讯作者：
Ploegh, Hidde L.
DOI：
10.1126/science.abb8032
发表时间：
2020-10-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mathieu C;Pappu RV;Taylor JP
通讯作者：
Taylor JP
影响因子：
4
作者：
Meyer, Hemmo;Weihl, Conrad C.
通讯作者：
Weihl, Conrad C.
影响因子：
4.8
作者：
Krisenko, Mariya O.;Higgins, Renee L.;Geahlen, Robert L.
通讯作者：
Geahlen, Robert L.
影响因子：
64.5
作者：
Buchan, J. Ross;Kolaitis, Regina-Maria;Parker, Roy
通讯作者：
Parker, Roy