Department of Pathology, New York University Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA.
Nat Rev Mol Cell Biol. 2013 Jun;14(6):369-81. doi: 10.1038/nrm3582. Epub 2013 May 9.
S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes use a family of F-box proteins as substrate adaptors to mediate the degradation of a large number of regulatory proteins involved in diverse processes. The dysregulation of SCF complexes and their substrates contributes to multiple pathologies. In the 14 years since the identification and annotation of the F-box protein family, the continued identification and characterization of novel substrates has greatly expanded our knowledge of the regulation of substrate targeting and the roles of F-box proteins in biological processes. Here, we focus on the evolution of our understanding of substrate recruitment by F-box proteins, the dysregulation of substrate recruitment in disease and potential avenues for F-box protein-directed disease therapies.
S 期激酶相关蛋白 1（SKP1）- 细胞周期蛋白 1（CUL1）-F-box 蛋白（SCF）泛素连接酶复合物利用一系列 F-box 蛋白作为底物衔接物来介导大量参与多种过程的调节蛋白的降解。SCF 复合物及其底物的失调导致多种病理。自 14 年前鉴定和注释 F-box 蛋白家族以来，不断鉴定和表征新的底物极大地扩展了我们对底物靶向调节以及 F-box 蛋白在生物过程中的作用的认识。在这里，我们重点介绍了我们对 F-box 蛋白招募底物的理解的演变、疾病中底物招募的失调以及 F-box 蛋白靶向疾病治疗的潜在途径。
