title: RIP1 modulates death receptor mediated apoptosis and autophagy in macrophages.
abstract: Macrophages are responsible for defending against diverse pathogens and play a crucial role in the innate immune system. Macrophage's lifespan is determined by homeostatic balance between survival and apoptosis. Here we report that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers both apoptosis and autophagy in human U937 cells. Inhibition of autophagy facilitates TRAIL-induced apoptosis, suggesting that autophagy of macrophages protects against TRAIL-induced apoptosis. TRAIL treatment influences the expression of death receptors, indicating that TRAIL-induced apoptosis and autophagy are mediated by death receptors. RIP1 ubiquitination and expression regulate apoptosis and autophagy. Furthermore, expression and bioactivity of the p43/41-caspase-8 variant are critical to TRAIL-induced autophagy and apoptosis. Knockdown of RIP1 suppresses autophagy in macrophage. These data demonstrate that RIP1 is essential for the regulation of death receptor mediated autophagy and apoptosis. The results in this study contribute to understanding the regulation of autophagy and apoptosis in macrophages, and shed lights on death receptor-targeted therapy for cancer, inflammation and autoimmune diseases.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Institute of Biomedical and Health Engineering Shenzhen Institutes of Advanced Technology, CAS, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Shilian
authors.initials: S
authors.lastname: Liu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China. Electronic address: zhengdx2008@gmail.com.
authors.forename: Dexian
authors.initials: D
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D016601:RNA-Binding Proteins / Q000378:metabolism*; D053218:Receptors, Death Domain / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects
chemical_list: C119724:AGFG1 protein, human; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D016328:NF-kappa B; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; D053181:Caspase 8; D020169:Caspases
keywords: Apoptosis; Autophagy; Death; RIP1; Tumor necrosis factor-related apoptosis-inducing ligand; Ubiquitination