title: Targeting A20 enhances TRAIL-induced apoptosis in hepatocellular carcinoma cells.
abstract: A20 was initially identified as a primary gene product following TNF α treatment in human umbilical vein endothelial cells. Increased A20 expression is associated with tumorigenesis in many cancers, whereas the loss of A20 function is linked to lymphoma. It has been reported that A20 protects cells from TRAIL-induced apoptosis; however, the mechanism by which A20 is involved is still largely unknown. Our results indicate that TRAIL induces the hepatocellular carcinoma apoptosis associated with A20 knockdown in a concentration-dependent manner. TRAIL-induced apoptosis requires p18 caspase-8 activation, and, the activation of caspase-8 is at least in part, due to the direct cleavage of RIP1 by A20 knockdown. These findings suggest that A20 modulates the sensitivity to TRAIL by RIP1 ubiquitination, thereby repressing the recruitment and activation of pro-caspase-8 into the active form caspase-8. Thus, our study suggests that A20 protects against TRAIL-induced apoptosis through the regulation of RIP1 ubiquitination.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, First Hospital of Jilin University, Jilin University, 71 Xinmin Street, Changchun 130021, China.
authors.forename: Bingfei
authors.initials: B
authors.lastname: Dong
authors.forename: Guoyue
authors.initials: G
authors.lastname: Lv
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Anita C
authors.initials: AC
authors.lastname: Bellail
authors.forename: Chunhai
authors.initials: C
authors.lastname: Hao
authors.forename: Guangyi
authors.initials: G
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D054875:Ubiquitination
chemical_list: C119724:AGFG1 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D053181:Caspase 8