1] Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. [2] The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou 215123, P. R. China. [3].
1] Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. [2].
Nat Rev Cancer. 2014 Apr;14(4):233-47. doi: 10.1038/nrc3700.
F-box proteins, which are the substrate-recognition subunits of SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes, have pivotal roles in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins. Dysregulation of F-box protein-mediated proteolysis leads to human malignancies. Notably, inhibitors that target F-box proteins have shown promising therapeutic potential, urging us to review the current understanding of how F-box proteins contribute to tumorigenesis. As the physiological functions for many of the 69 putative F-box proteins remain elusive, additional genetic and mechanistic studies will help to define the role of each F-box protein in tumorigenesis, thereby paving the road for the rational design of F-box protein-targeted anticancer therapies.
F-box 蛋白是 SKP1-cullin1-F-box 蛋白（SCF）E3 连接酶复合物的底物识别亚基，通过靶蛋白的泛素化和随后的降解，在多种细胞过程中发挥关键作用。F-box 蛋白介导的蛋白水解的失调导致人类恶性肿瘤。值得注意的是，靶向 F-box 蛋白的抑制剂显示出有希望的治疗潜力，促使我们回顾当前对 F-box 蛋白如何促进肿瘤发生的理解。由于许多 69 种推定的 F-box 蛋白的生理功能仍然难以捉摸，因此需要进行更多的遗传和机制研究，以确定每个 F-box 蛋白在肿瘤发生中的作用，从而为合理设计针对 F-box 蛋白的抗癌治疗铺平道路。
