title: Ro52/SSA sensitizes cells to death receptor-induced apoptosis by down-regulating c-FLIP(L).
abstract: Ro52/SSA is an autoantigen that presents in patients with SS (Sjögren's syndrome) and SLE (systemic lupus erythematosus). It increases cell death and redistributes itself to apoptotic blebs, but its pro-apoptotic function has not been completely identified. Overexpression of Ro52/SSA promoted cell apoptosis induced by DR (death receptor) in caspase-8-dependent manner. Ro52/SSA expression down-regulated c-FLIP(L) [cellular (Fas-associated death domain)-like interleukin 1β-converting enzyme-inhibitory protein long form] expression, and Ro52/SSA siRNAs (small interfering RNAs) increased c-FLIP(L) production, indicating that Ro52/SSA plays a role in c-FLIP(L) regulation. Ro52/SSA negatively regulated c-FLIP(L) transcriptional level probably by suppressing NF-κB (nuclear factor κB) signalling. The data suggest that Ro52/SSA is involved in DR-mediated apoptosis by regulating c-FLIP(L).
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Xuguo
authors.initials: X
authors.lastname: Zhu
authors.forename: Yiting
authors.initials: Y
authors.lastname: Qiao
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Wu
authors.initials: W
authors.lastname: Yin
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D053218:Receptors, Death Domain / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099207:SS-A Antigen
chemical_list: D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053181:Caspase 8; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D053218:Receptors, Death Domain; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C506386:CFLAR protein, human