Ha Hyun Ji, Park Hyun Ho
College of Pharmacy, Chung-Ang University, Seoul, 06974, South Korea.
Mol Biol Rep. 2018 Dec;45(6):1715-1722. doi: 10.1007/s11033-018-4314-5. Epub 2018 Aug 23.
The RIPoptosome, composed of RIP1 and caspase-8, plays an important role in the regulation of apoptosis and necroptosis; however, the mechanism of complex formation by oligomerization and how the caspase-activating process and necroptosis are mediated by the formation of the RIPoptosome is not well-understood. This study revealed that the assembly mechanism of the RIPoptosome core is dependent on salt concentration and not on pH and time. In addition, we demonstrated that three RIP1 mutations, E626K, M637K, and S657K, have dominant negative effects. These dominant negative mutations in RIP1 may have potential applications in therapeutic intervention.
由RIP1和半胱天冬酶-8组成的RIPoptosome在细胞凋亡和坏死性凋亡的调控中起重要作用；然而，寡聚化形成复合物的机制以及RIPoptosome的形成如何介导半胱天冬酶激活过程和坏死性凋亡尚不清楚。本研究表明，RIPoptosome核心的组装机制取决于盐浓度，而不取决于pH值和时间。此外，我们证明了三个RIP1突变E626K、M637K和S657K具有显性负效应。RIP1中的这些显性负突变可能在治疗干预中有潜在应用。
