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

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2020 Jun 10

PMID 32513610

Citations 32

Authors

Michael J Emanuele

Taylor P Enrico

Ryan D Mouery

Danit Wasserman

Sapir Nachum

Amit Tzur

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Cdk1 and PP2A constitute a molecular switch controlling orderly degradation of atypical E2Fs.

Nachum-Raines S, Gamliel N, Wasserman D, Qassem N, Sher I, Guez-Haddad J bioRxiv. 2025; .

PMID: 40027684 PMC: 11870630. DOI: 10.1101/2025.02.23.639703.

The SETDB1-PC4-UPF1 post-transcriptional machinery controls periodic degradation of CENPF mRNA and maintains mitotic progression.

Pan Q, Luo P, Qiu Y, Hu K, Lin L, Zhang H Cell Death Differ. 2025; .

PMID: 40016337 DOI: 10.1038/s41418-025-01465-z.

Structural mechanism for recognition of E2F1 by the ubiquitin ligase adaptor Cyclin F.

Ngoi P, Wang X, Putta S, Da Luz R, Serrao V, Emanuele M bioRxiv. 2025; .

PMID: 39868286 PMC: 11761524. DOI: 10.1101/2025.01.15.633208.

miR-5100 Overexpression Inhibits Prostate Cancer Progression by Inducing Cell Cycle Arrest and Targeting E2F7.

Zhang A, Deng W, Shang H, Wu J, Zhang Y, Zhuang Q Curr Issues Mol Biol. 2024; 46(11):13151-13164.

PMID: 39590378 PMC: 11592579. DOI: 10.3390/cimb46110784.

Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Goleij P, Pourali G, Raisi A, Ravaei F, Golestan S, Abed A Mol Neurobiol. 2024; 62(2):1726-1755.

PMID: 39023794 DOI: 10.1007/s12035-024-04316-z.

References

Lukas C, Sorensen C, Kramer E, Santoni-Rugiu E, Lindeneg C, Peters J . Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex. Nature. 1999; 401(6755):815-8. DOI: 10.1038/44611. View

Fang G, Yu H, Kirschner M . The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev. 1998; 12(12):1871-83. PMC: 316912. DOI: 10.1101/gad.12.12.1871. View

Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A . SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol. 2001; 21(21):7403-15. PMC: 99913. DOI: 10.1128/MCB.21.21.7403-7415.2001. View

Bembenek J, Yu H . Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a. J Biol Chem. 2001; 276(51):48237-42. DOI: 10.1074/jbc.M108126200. View

Di Stefano L, Jensen M, Helin K . E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes. EMBO J. 2003; 22(23):6289-98. PMC: 291854. DOI: 10.1093/emboj/cdg613. View

Floyd S, Pines J, Lindon C . APC/C Cdh1 targets aurora kinase to control reorganization of the mitotic spindle at anaphase. Curr Biol. 2008; 18(21):1649-58. DOI: 10.1016/j.cub.2008.09.058. View

Chen X, Muller G, Quaas M, Fischer M, Han N, Stutchbury B . The forkhead transcription factor FOXM1 controls cell cycle-dependent gene expression through an atypical chromatin binding mechanism. Mol Cell Biol. 2012; 33(2):227-36. PMC: 3554121. DOI: 10.1128/MCB.00881-12. View

Ciechanover A . Tracing the history of the ubiquitin proteolytic system: the pioneering article. Biochem Biophys Res Commun. 2009; 387(1):1-10. DOI: 10.1016/j.bbrc.2009.06.065. View

Elia A, Boardman A, Wang D, Huttlin E, Everley R, Dephoure N . Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response. Mol Cell. 2015; 59(5):867-81. PMC: 4560960. DOI: 10.1016/j.molcel.2015.05.006. View

10.

King R, Peters J, Tugendreich S, Rolfe M, Hieter P, Kirschner M . A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell. 1995; 81(2):279-88. DOI: 10.1016/0092-8674(95)90338-0. View

11.

Zou H, McGarry T, Bernal T, Kirschner M . Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science. 1999; 285(5426):418-22. DOI: 10.1126/science.285.5426.418. View

12.

Kramer E, Gieffers C, Holzl G, Hengstschlager M, Peters J . Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. Curr Biol. 1998; 8(22):1207-10. DOI: 10.1016/s0960-9822(07)00510-6. View

13.

Bornstein G, Bloom J, Sitry-Shevah D, Nakayama K, Pagano M, Hershko A . Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. J Biol Chem. 2003; 278(28):25752-7. DOI: 10.1074/jbc.M301774200. View

14.

Fukushima H, Ogura K, Wan L, Lu Y, Li V, Gao D . SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Rep. 2013; 4(4):803-16. PMC: 3839583. DOI: 10.1016/j.celrep.2013.07.031. View

15.

Hansen M, Desai R, Simpson M, Weinberger L . Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability. Cell Syst. 2018; 7(4):384-397.e6. PMC: 6202163. DOI: 10.1016/j.cels.2018.08.002. View

16.

Shirayama M, Toth A, Galova M, Nasmyth K . APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature. 2000; 402(6758):203-7. DOI: 10.1038/46080. View

17.

Sullivan M, Morgan D . Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol. 2007; 8(11):894-903. DOI: 10.1038/nrm2276. View

18.

Cuitino M, Pecot T, Sun D, Kladney R, Okano-Uchida T, Shinde N . Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation. Cell Rep. 2019; 27(12):3547-3560.e5. PMC: 6673649. DOI: 10.1016/j.celrep.2019.05.004. View

19.

Li J, Ran C, Li E, Gordon F, Comstock G, Siddiqui H . Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev Cell. 2008; 14(1):62-75. PMC: 2253677. DOI: 10.1016/j.devcel.2007.10.017. View

20.

Koseoglu M, Graves L, Marzluff W . Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase. Mol Cell Biol. 2008; 28(14):4469-79. PMC: 2447125. DOI: 10.1128/MCB.01416-07. View