Programmed cell death(PCD)is characterized as a cell death pathway governed by specific gene-encoding requirements,plays crucial roles in the homeostasis and innate immunity of organisms,and serves as both a pathogeni...Programmed cell death(PCD)is characterized as a cell death pathway governed by specific gene-encoding requirements,plays crucial roles in the homeostasis and innate immunity of organisms,and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases.Z-DNA-binding protein 1(ZBP1)functions as a cytosolic nucleic acid sensor,utilizing its unique Zαdomains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif(RHIM)domains to sense or bind specific signaling molecules,thereby exerting regulatory effects on various forms of PCD.ZBP1 is involved in apoptosis,necroptosis,pyroptosis,and PANoptosis and interacts with molecules,such as receptor-interacting protein kinase 3(RIPK3),to influence cell fate under various pathological conditions.It plays a crucial role in regulating PCD during infections,inflammatory and neurological diseases,cancers,and other conditions,affecting disease onset and progression.Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions.This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD,along with the potential therapeutic implications of ZBP1 in these contexts.Ongoing research on ZBP1 is being refined across various disease models,and these advancements may provide novel insights for studies focusing on PCD,potentially leading to new therapeutic options for related diseases.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.82273559,82103757,and 82073473)the Department of Science and Technology of Sichuan Province(No.2022YFQ0054)Sichuan Natural Science Foundation Project(No.2023NSFSC1554)
文摘Programmed cell death(PCD)is characterized as a cell death pathway governed by specific gene-encoding requirements,plays crucial roles in the homeostasis and innate immunity of organisms,and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases.Z-DNA-binding protein 1(ZBP1)functions as a cytosolic nucleic acid sensor,utilizing its unique Zαdomains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif(RHIM)domains to sense or bind specific signaling molecules,thereby exerting regulatory effects on various forms of PCD.ZBP1 is involved in apoptosis,necroptosis,pyroptosis,and PANoptosis and interacts with molecules,such as receptor-interacting protein kinase 3(RIPK3),to influence cell fate under various pathological conditions.It plays a crucial role in regulating PCD during infections,inflammatory and neurological diseases,cancers,and other conditions,affecting disease onset and progression.Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions.This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD,along with the potential therapeutic implications of ZBP1 in these contexts.Ongoing research on ZBP1 is being refined across various disease models,and these advancements may provide novel insights for studies focusing on PCD,potentially leading to new therapeutic options for related diseases.
