美国圣裘德儿童研究医院J. Paul Taylor研究组表明G3BP1 的泛素化以特定环境的方式介导应力颗粒分解。相关论文发表在2021年6月25日出版的《科学》杂志上。

损伤分解与一些疾病有关，包括肌萎缩侧索硬化、额颞叶痴呆和多系统蛋白病。使用培养的人类细胞，他们发现压力颗粒的分解是依赖于环境的：特别是在热休克的情况下，分解需要 G3BP1 的泛素化，G3BP1 是压力颗粒 RNA 蛋白网络中的中心蛋白。

他们发现泛素化 G3BP1 与内质网相关蛋白 FAF2 相互作用，FAF2 与泛素依赖性分离酶 p97/VCP（含 valosin 蛋白）结合。因此，靶向 G3BP1 削弱了应力颗粒特异性相互作用网络，导致颗粒分解。

研究人员表示，压力颗粒是由 RNA 和蛋白质组成的动态、可逆的凝聚物，它们在真核细胞中组装以响应各种压力源，通常在压力消除后分解。应力颗粒的组成和组装是众所周知的，但对控制分解的机制知之甚少。

附：英文原文

Title: Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner

Author: Youngdae Gwon, Brian A. Maxwell, Regina-Maria Kolaitis, Peipei Zhang, Hong Joo Kim, J. Paul Taylor

Issue&Volume: 2021/06/25

Abstract: 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.

DOI: 10.1126/science.abf6548

Source: https://science.sciencemag.org/content/372/6549/eabf6548