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The Cell Cycle Control System

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The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

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Cell cycle oscillators underlying orderly proteolysis of E2F8.

Danit Wasserman¹, Sapir Nachum¹, Meital Cohen¹

¹Faculty of Life Sciences and Institute of Nanotechnology and Advanced Materials, Bar-llan University, Ramat-Gan 5290002, Israel.

Molecular Biology of the Cell

|January 30, 2020

Summary

Researchers uncovered how the E2F8 protein

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Area of Science:

Molecular Biology
Cell Cycle Regulation
Ubiquitination and Proteolysis

Background:

E2F8 acts as a transcriptional repressor, influencing cell cycle, apoptosis, and cancer.
E2F8 is a known target of the APC/C ubiquitin ligase, but its cell cycle-specific regulation is unclear.

Purpose of the Study:

To elucidate the dynamic control mechanisms of E2F8 throughout the entire cell cycle.
To understand the interplay between E2F8 phosphorylation, ubiquitination, and transcriptional activity.

Main Methods:

Utilized novel human cell-free systems to model inter-mitotic, G1, and prometaphase-to-G1 transitions.
Investigated E2F8 degradation kinetics and regulation by APC/C^Cdh1 and Cyclin F.

Main Results:

Identified a dephosphorylation switch that coordinates E2F8 degradation with mitotic exit and APC/C^Cdh1 activation.
Revealed differential E2F8 proteolysis rates in G1, explaining its late G1 accumulation.
Demonstrated Cyclin F's role in regulating E2F8 during the G2 phase.

Conclusions:

Established a comprehensive model for E2F8 regulation across the cell cycle.
Highlighted extensive coordination between phosphorylation, ubiquitination, and transcription in mammalian cell cycle control.