铁代谢与蛋白质泛素化-降解调控研究进展

Recent advance on crosstalk between iron metabolism and cellular protein ubiquitylation and degradation

铁元素为几乎所有的生命体所必需,维持铁代谢稳态对机体的正常功能至关重要。铁代谢紊乱与人类多种疾病的发生和发展有关。已知铁代谢稳态受到一系列参与铁代谢环节的关键蛋白质,如IRP2等的精确调节。这些重要蛋白质的稳定性、生理活性的动态变化及其协调作用是细胞维持铁代谢平衡的分子基础。除了转录和转录后水平的调控,泛素化等翻译后修饰方式和蛋白质降解是细胞精确调控参与铁代谢的蛋白质的水平及功能普遍而有效的方式之一;同时,细胞的铁代谢状态也影响细胞内参与泛素化等翻译后修饰途径的酶类的活性和稳定性,从而在铁代谢和蛋白质修饰-降解途径之间形成反馈机制,实时和动态地完成对细胞内铁代谢水平的精确调控。就相关领域的最新进展作简要综述。

As iron is one of the essential metal elements for life, maintaining homeostasis of iron metabolism is crucial for any cell to survive and function normally. Perturbed iron metabolism has been a known cause of many human diseases. Delicate regulatory mechanisms have been evolved to maintain iron homeostasis at both organismand cell level. Previously, we and others have shown that heine, as a major form of iron existing in cell, regulates folding, ubiquitylation and/or degradation of heine-binding proteins, such as IRP2 and ATE1 etc. in both prokaryotes and eukaryotes. There were now most recent reports that FBXL5, an F-box ubiquitin ligase, ubiquitylates iron regulatory protein 2 （IRP2） in an iron-dependent manner, while FBXL5 itself is stabilized by iron at elevated level. Here we review advances and present our perspectives of research into crosstalk between iron metabolism and cellular protein ubiquitylation and proteolysis.