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Updated: May 13, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
The ubiquitin proteasome system - implications for cell cycle control and the targeted treatment of cancer
Florian Bassermann1, Ruth Eichner, Michele Pagano
1Department of Medicine III, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
Abstract:
Two families of E3 ubiquitin ligases are prominent in cell cycle regulation and mediate the timely and precise ubiquitin-proteasome-dependent degradation of key cell cycle proteins: the SCF (Skp1/Cul1/F-box protein) complex and the APC/C (anaphase promoting complex or cyclosome). While certain SCF ligases drive cell cycle progression throughout the cell cycle, APC/C (in complex with either of two substrate recruiting proteins: Cdc20 and Cdh1) orchestrates exit from mitosis (APC/C(Cdc20)) and establishes a stable G1 phase (APC/C(Cdh1)). Upon DNA damage or perturbation of the normal cell cycle, both ligases are involved in checkpoint activation. Mechanistic insight into these processes has significantly improved over the last ten years, largely due to a better understanding of APC/C and the functional characterization of multiple F-box proteins, the variable substrate recruiting components of SCF ligases. Here, we review the role of SCF- and APC/C-mediated ubiquitylation in the normal and perturbed cell cycle and discuss potential clinical implications of SCF and APC/C functions. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.
Insights
The SCF and APC/C E3 ubiquitin ligases control cell cycle progression and DNA damage responses. Their roles in ubiquitylation are crucial for cell cycle regulation and have potential clinical implications.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- The SCF (Skp1/Cul1/F-box protein) complex and the APC/C (anaphase promoting complex or cyclosome) are key E3 ubiquitin ligases.
- These ligases are central to cell cycle regulation through targeted protein degradation.
- Both SCF and APC/C play roles in checkpoint activation during cell cycle stress.
Purpose of the Study:
- To review the function of SCF and APC/C ligases in normal and perturbed cell cycles.
- To discuss the clinical relevance of these ubiquitin ligase pathways.
- To highlight recent advancements in understanding these complexes.
Main Methods:
- Literature review of studies on SCF and APC/C ubiquitin ligases.
- Analysis of mechanistic insights into ubiquitylation processes.
- Discussion of functional characterization of F-box proteins and APC/C co-activators.
Main Results:
- SCF ligases drive cell cycle progression.
- APC/C(Cdc20) mediates mitotic exit, while APC/C(Cdh1) establishes G1 phase.
- Both ligases are implicated in cell cycle checkpoint activation.
Conclusions:
- SCF and APC/C-mediated ubiquitylation are critical for cell cycle control.
- Dysregulation of these pathways may have clinical implications.
- Continued research is vital for understanding their roles in health and disease.
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