Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins.
Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins.
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DOI：
10.1098/rsob.130131
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发表时间：
2013-10-09
期刊：
影响因子：
5.8
通讯作者：
Laman H
中科院分区：
文献类型：
--
作者：
Nelson DE;Randle SJ;Laman H
F-box蛋白（FBPs）是Skp 1-cullin 1-FBP（SCF）型E3泛素连接酶的底物募集亚基。到目前为止，已经在人类中鉴定了69种FBPs，但仅鉴定了少数几种泛素化底物，大多数FBPs仍然是“蛋白质”。近年来，越来越多的工作已经确定了约12%的人类FBPs的非规范，SCF独立的角色。这些非典型FBPs影响的过程多种多样的转录，细胞周期调控，线粒体动力学和细胞内运输。在这里，我们提供了一个FBPs的一般审查，特别强调这些扩展的功能。我们回顾Fbxo 7作为这个特殊群体的一个范例，因为它在SCF和非SCF复合物中具有明确的作用。我们回顾了它作为细胞周期调节剂的功能，通过其稳定p27蛋白和Cdk 6复合物的能力，以及作为蛋白酶体调节剂，由于其与PI 31的高亲和力结合。我们还强调了我们对Fbxo 7在帕金森病中功能的理解的最新进展，在帕金森病中，Fbxo 7与PINK 1和Parkin一起调节线粒体自噬。我们假设，一些特殊的FBPs作为平台，无缝地衔接其规范和非规范的功能，以整合不同的细胞通路，并连接它们的调节。
F-box proteins (FBPs) are substrate-recruiting subunits of Skp1-cullin1-FBP (SCF)-type E3 ubiquitin ligases. To date, 69 FBPs have been identified in humans, but ubiquitinated substrates have only been identified for a few, with the majority of FBPs remaining ‘orphans’. In recent years, a growing body of work has identified non-canonical, SCF-independent roles for about 12% of the human FBPs. These atypical FBPs affect processes as diverse as transcription, cell cycle regulation, mitochondrial dynamics and intracellular trafficking. Here, we provide a general review of FBPs, with a particular emphasis on these expanded functions. We review Fbxo7 as an exemplar of this special group as it has well-defined roles in both SCF and non-SCF complexes. We review its function as a cell cycle regulator, via its ability to stabilize p27 protein and Cdk6 complexes, and as a proteasome regulator, owing to its high affinity binding to PI31. We also highlight recent advances in our understanding of Fbxo7 function in Parkinson's disease, where it functions in the regulation of mitophagy with PINK1 and Parkin. We postulate that a few extraordinary FBPs act as platforms that seamlessly segue their canonical and non-canonical functions to integrate different cellular pathways and link their regulation.
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