Complex Cartography: Regulation of E2F Transcription Factors by Cyclin F and Ubiquitin

Michael J. Emanuele, Taylor P. Enrico, Ryan D. Mouery, Danit Wasserman, Sapir Nachum, Amit Tzur

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations


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.

Original languageEnglish
Pages (from-to)640-652
Number of pages13
JournalTrends in Cell Biology
Issue number8
StatePublished - Aug 2020

Bibliographical note

Funding Information:
The Emanuele laboratory is supported by the UNC University Cancer Research Fund, National Institutes of Health ( R01GM120309 , R01GM134231 ), American Cancer Society (RSG-18-220-01-TBG), and donations from the Brookside Foundation. The Tzur laboratory is supported by the Israel Science Foundation (ISF) (2038/19).

Publisher Copyright:
© 2020 Elsevier Ltd


  • APC/C (Cdh1)
  • E2F
  • SCF (Cyclin F)
  • cell cycle
  • transcription
  • ubiquitin


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