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FK506结合蛋白51整合适应途径:FKBP51塑造对环境变化的反应性。

FK506 binding protein 51 integrates pathways of adaptation: FKBP51 shapes the reactivity to environmental change.

作者信息

Rein Theo

机构信息

Department of Translational Science in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.

出版信息

Bioessays. 2016 Sep;38(9):894-902. doi: 10.1002/bies.201600050. Epub 2016 Jul 4.

Abstract

This review portraits FK506 binding protein (FKBP) 51 as "reactivity protein" and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation. Adaptation is a fundamental process that enables unicellular and multicellular organisms to adjust their molecular circuits and structural conditions in reaction to environmental changes threatening their homeostasis. FKBP51 is known as chaperone and co-chaperone of heat shock protein (HSP) 90, thus involved in processes ensuring correct protein folding in response to proteotoxic stress. In mammals, FKBP51 both shapes the stress response and is calibrated by the stress levels through an ultrashort molecular feedback loop. More recently, it has been linked to several intracellular pathways related to the reactivity to drug exposure and stress. Through its role in autophagy and DNA methylation in particular it influences adaptive pathways, possibly also in a transgenerational fashion. Also see the video abstract here.

摘要

本综述将FK506结合蛋白(FKBP)51描述为“反应性蛋白”,并整理了近期的出版物,以发展FKBP51作为不同适应水平促成因素的概念。适应是一个基本过程,使单细胞和多细胞生物能够在面对威胁其体内平衡的环境变化时调整其分子回路和结构条件。FKBP51作为热休克蛋白(HSP)90的伴侣蛋白和共伴侣蛋白而为人所知,因此参与了确保蛋白质在蛋白毒性应激下正确折叠的过程。在哺乳动物中,FKBP51既塑造应激反应,又通过一个超短分子反馈回路由应激水平进行校准。最近,它已与几种与药物暴露和应激反应性相关的细胞内途径联系起来。特别是通过其在自噬和DNA甲基化中的作用,它影响适应性途径,也可能以跨代方式产生影响。另请参阅此处的视频摘要。

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