Randle Suzanne J, Laman Heike
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Semin Cancer Biol. 2016 Feb;36:3-17. doi: 10.1016/j.semcancer.2015.09.013. Epub 2015 Sep 28.
F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention.
F盒蛋白（FBP）是Skp1-Cul1-FBP（SCF）型E3泛素连接酶的底物特异性亚基，负责指导众多细胞功能所必需蛋白质的泛素化。由于其具有调节癌基因和肿瘤抑制基因表达及活性的能力，FBP自身在癌症发生发展过程中发挥着重要作用。在本综述中，我们全面概述了FBP及其靶点，及其与癌细胞生物学特征的相互作用，包括对增殖、表观遗传学、迁移和侵袭、代谢、血管生成、细胞死亡及DNA损伤反应的调节。结果表明，每个癌症特征都有多个FBP汇聚于共同的信号枢纽或反应途径。我们还强调了SCF型连接酶与其他泛素连接酶之间复杂的调控相互作用。我们提出六个高度相互关联的FBP影响多个癌症特征，它们可能是合理的治疗干预候选靶点。
