SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production
SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production
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DOI：
10.1016/j.bbrc.2011.12.010
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发表时间：
2012-01-06
影响因子：
3.1
通讯作者：
Kawano, Seiji
中科院分区：
文献类型：
--
作者：
Jauharoh, Siti Nur Aisyah;Saegusa, Jun;Kawano, Seiji
SS-A/Ro 52（Ro 52）是系统性自身免疫性疾病（如系统性红斑狼疮和干燥综合征）中的自身抗原，具有E3连接酶活性以使蛋白质泛素化，从而保护免受病毒感染。为了研究Ro 52在应激过程中的作用，我们通过siRo 52转染在HeLa细胞中瞬时敲除它。我们发现，Ro 52（低）HeLa细胞比野生型HeLa细胞更显着抗凋亡时，刺激过氧化氢或二酰胺诱导的氧化应激，IFN-α，IFN-γ和抗Fas抗体，依托泊苷，或γ-辐射。Ro 52介导的HeLa细胞凋亡不受p53蛋白水平的影响。在HeLa细胞中耗尽Ro 52导致Bcl-2，而不是其他Bcl-2家族分子上调。总之，我们的数据表明，Ro 52是一种通用的促凋亡分子，其促凋亡作用不依赖于p53，而是通过抗凋亡蛋白Bcl-2的负调控发挥作用。这些发现揭示了Ro 52对细胞内免疫重要的新生理作用。(C)2011 Elsevier Inc. All rights reserved.
SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52(low) HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H2O2- or diamide-induced oxidative stress, IFN-alpha, IFN-gamma and anti-Fas antibody, etoposide, or gamma-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity. (C) 2011 Elsevier Inc. All rights reserved.