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首页> 外文期刊>Journal of Molecular Biology >Alpha-Synuclein Is a Target of Fic-Mediated Adenylylation/AMPylation: Possible Implications for Parkinson's Disease
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Alpha-Synuclein Is a Target of Fic-Mediated Adenylylation/AMPylation: Possible Implications for Parkinson's Disease

机译：α-突触核蛋白是FIC介导的腺苷酸/氨基化的靶标：对帕金森病的可能影响

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During disease, cells experience various stresses that manifest as an accumulation of misfolded proteins and eventually lead to cell death. To combat this stress, cells activate a pathway called unfolded protein response that functions to maintain endoplasmic reticulum (ER) homeostasis and determines cell fate. We recently reported a hitherto unknown mechanism of regulating ER stress via a novel post-translational modification called Fic-mediatedadenylylation/AMPylation. Specifically, we showed that the human Fic (filamentation induced by cAMP) protein, HYPE/FicD, catalyzes the addition of an adenosine monophosphate (AMP) to the ER chaperone, BiP, to alter the cell's unfolded protein response-mediated response to misfolded proteins. Here, we report that we have now identified a second target for HYPE alpha-synuclein (alpha Syn), a presynaptic protein involved in Parkinson's disease. Aggregated alpha Syn has been shown to induce ER stress and elicit neurotoxicity in Parkinson's disease models. We show that HYPE adenylylates alpha Syn and reduces phenotypes associated with alpha Syn aggregation invitro, suggesting a possible mechanism by which cells cope with alpha Syn toxicity. (C) 2019 Elsevier Ltd. All rights reserved.
机译：在疾病期间，细胞体验了各种压力，表现为被错误折叠的蛋白质的积累，最终导致细胞死亡。为了对抗这种应力，细胞激活称为展开蛋白质反应的途径，其用于保持内质网（ER）稳态并确定细胞命运。我们最近通过一种名为FIC - Medientiallation /氨基化的新型翻译后修饰来调节ER压力的迄今为止的调节机制。具体而言，我们表明，人FIC（CAMP诱导的细纱）蛋白质，炒作/ FICD，催化添加腺苷一磷酸（AMP）的腺苷（AMP），以改变细胞的展开蛋白响应介导的对错误折叠的蛋白质的反应。在这里，我们报告说我们现在已经确定了炒作α-突触核蛋白（Alpha Syn）的第二个靶标，该蛋白质涉及帕金森病的突触蛋白。综合alpha Syn已被证明在帕金森病模型中诱导ER应激和源神经毒性。我们表明，炒作腺苷酸αSYN并减少与α1AN聚集invitro的表型，表明细胞应对α1SYN毒性的可能机制。 （c）2019 Elsevier Ltd.保留所有权利。

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