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2篇 您的检索式:作者名="LIU Erpeng"
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1HSPA8 acts as an amyloidase to suppress necroptosis by inhibiting and reversing functional amyloid formation显示文摘Ultra-stable fibrous structure is a hallmark of amyloids.In contrast to canonical disease-related amyloids,emerging research indicates that a significant number of cellular amyloids,termed‘functional amyloids’,contribute to signal transduction as temporal signaling hubs in humans.However,it is unclear how these functional amyloids are effectively disassembled to terminate signal transduction.RHIM motif-containing amyloids,the largest functional amyloid family discovered thus far,play an important role in mediating necroptosis signal transduction in mammalian cells.Here,we identify heat shock protein family A member 8(HSPA8)as a new type of enzyme—which we name as‘amyloidase’—that directly disassembles RHIM-amyloids to inhibit necroptosis signaling in cells and mice.Different from its role in chaperone-mediated autophagy where it selects substrates containing a KFERQ-like motif,HSPA8 specifically recognizes RHIM-containing proteins through a hydrophobic hexapeptide motif N(X_(1))φ(X_(3)).The SBD domain of HSPA8 interacts with RHIM-containing proteins,preventing proximate RHIM monomers from stacking into functional fibrils;furthermore,with the NBD domain supplying energy via ATP hydrolysis,HSPA8 breaks down pre-formed RHIM-amyloids into non-functional monomers.Notably,HSPA8’s amyloidase activity in disassembling functional RHIM-amyloids does not require its co-chaperone system.Using this amyloidase activity,HSPA8 reverses the initiator RHIM-amyloids(formed by RIP1,ZBP1,and TRIF)to prevent necroptosis initiation,and reverses RIP3-amyloid to prevent necroptosis execution,thus eliminating multi-level RHIM-amyloids to effectively prevent spontaneous necroptosis activation.The discovery that HSPA8 acts as an amyloidase dismantling functional amyloids provides a fundamental understanding of the reversibility nature of functional amyloids,a property distinguishing them from disease-related amyloids that are unbreakable in vivo.Erpeng Wu Wenyan He Chenlu Wu Zhangcheng Chen Shijie Zhou Xialian Wu Zhiheng Hu Kelong Jia Jiasong Pan Limin Wang Jie Qin Dan Liu Junxia Lu Huayi Wang Jixi Li Sheng Wang Liming Sun 2023Cell Research2023,33,11:0
2Human capital, Social Capital and the Informal Employment of Floating Population显示文摘LIU Yiwei LIU Erpeng 2015International English Education Research2015,,12:0
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