title: The ubiquitin proteasome system - implications for cell cycle control and the targeted treatment of cancer.
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.
authors: Department of Medicine III, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. Electronic address: florian.bassermann@lrz.tum.de.
authors: Florian
authors: F
authors: Bassermann
authors: Ruth
authors: R
authors: Eichner
authors: Michele
authors: M
authors: Pagano
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D006801:Humans; D008938:Mitosis / Q000502:physiology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D025801:Ubiquitin / Q000502:physiology*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: APC/C; Cancer; Cell cycle; F-box; SCF complex; Ubiquitin proteasome system