The E2F family of transcriptional regulators sits at the center of cell cycle gene expression and plays vital roles in normal and cancer cell cycles. Whereas control of E2Fs by the retinoblastoma family of proteins is well established, much less is known about their regulation by ubiquitin pathways. Recent studies placed the Skp1-Cul1-F-box-protein (SCF) family of E3 ubiquitin ligases with the F-box protein Cyclin F at the center of E2F regulation, demonstrating temporal proteolysis of both activator and atypical repressor E2Fs. Importantly, these E2F members, in particular activator E2F1 and repressors E2F7 and E2F8, form a feedback circuit at the crossroads of cell cycle and cell death. Moreover, Cyclin F functions in a reciprocal circuit with the cell cycle E3 ligase anaphase-promoting complex/cyclosome (APC/C), which also controls E2F7 and E2F8. This review focuses on the complex contours of feedback within this circuit, highlighting the deep crosstalk between E2F, SCF-Cyclin F, and APC/C in regulating the oscillator underlying human cell cycles.

E2F 转录调节因子家族位于细胞周期基因表达的中心，在正常和癌细胞周期中发挥着至关重要的作用。尽管视网膜母细胞瘤蛋白家族对 E2F 的控制已得到充分证实，但人们对泛素途径对 E2F 的调节知之甚少。最近的研究将E3 泛素连接酶的S kp1- C ul1 - F -box 蛋白 (SCF) 家族与 F-box 蛋白 Cyclin F 置于 E2F 调节的中心，证明了激活剂和非典型阻遏物 E2F 的瞬时蛋白水解。重要的是，这些 E2F 成员，特别是激活子 E2F1 和阻遏子 E2F7 和 E2F8，在细胞周期和细胞死亡的十字路口形成反馈回路。此外，细胞周期蛋白 F 与细胞周期 E3 连接酶促进后期复合物/细胞周期体 (APC/C) 一起发挥作用，该酶还控制E2F7和E2F8。本综述重点关注该电路内反馈的复杂轮廓，强调 E2F、SCF-Cyclin F 和 APC/C 在调节人体细胞周期的振荡器方面的深层串扰。