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Ro52/SSA sensitizes cells to death receptor-induced apoptosis by down-regulating c-FLIP(L)

Authors

  • Jing Zhang,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Lei Fang,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Xuguo Zhu,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Yiting Qiao,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Mei Yu,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Lu Wang,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Yuan Chen,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Wu Yin,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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  • Zi-Chun Hua

    Corresponding author
    1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210093, Peoples Republic of China and Changzhou HighTech Research Institute of Nanjing University, Changzhou 213164, Peoples Republic of China
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To whom correspondence should be addressed (email zchua@nju.edu.cn).

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).

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