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The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint. The past few years have witnessed significant progress in understanding the quantitative mechanisms underlying these varied APC/C functions. This review integrates the overall functions and properties of the APC/C with mechanistic insights gained from recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C complexes.
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http://dx.doi.org/10.1098/rsob.170204 | DOI Listing |
BMB Rep
September 2025
Department of Molecular Biology, Dankook University, Cheonan 31116, Korea.
Anaphase-promoting complex/cyclosome (APC/C) regulates the cell cycle by destruction of target proteins ubiquitination. However, understanding the control of APC/C has remained elusive. We identify APC2, the catalytic core subunit of APC/C, as a binding partner of active regulator of SIRT1 (AROS).
View Article and Find Full Text PDFMol Phylogenet Evol
September 2025
Laboratory of Biodiversity and Evolution of Protozoa, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China. Electronic address:
Early-branching eukaryotes are associated with the early branching events during eukaryogenesis. Understanding their genomic diversity and evolution can provide insights into the origin and speciation of eukaryotes. Ciliated protists (ciliates) are a group of early-branching unicellular eukaryotes with a high biodiversity, making them excellent models for evolutionary studies.
View Article and Find Full Text PDFElife
September 2025
Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
E3 ubiquitin ligases engage their substrates via 'degrons' - short linear motifs typically located within intrinsically disordered regions of substrates. As these enzymes are large, multi-subunit complexes that generally lack natural small-molecule ligands and are difficult to inhibit via conventional means, alternative strategies are needed to target them in diseases, and peptide-based inhibitors derived from degrons represent a promising approach. Here we explore peptide inhibitors of Cdc20, a substrate-recognition subunit and activator of the E3 ubiquitin ligase the anaphase-promoting complex/cyclosome (APC/C) that is essential in mitosis and consequently of interest as an anti-cancer target.
View Article and Find Full Text PDFZygote
September 2025
Field Centre for Sustainable Agriculture, Faculty of Agriculture, Niigata University, Niigata, Japan.
Aneuploidy in oocytes is a leading cause of implantation failure, miscarriage and congenital disorders. During meiosis, proper timing of chromosome segregation is regulated by the spindle assembly checkpoint (SAC) and the anaphase-promoting complex/cyclosome (APC/C). However, how pharmacological manipulation of these regulatory pathways affects aneuploidy remains incompletely understood.
View Article and Find Full Text PDFCell Immunol
September 2025
Departments of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.. Electronic address:
Acute lung injury (ALI) is a respiratory disease induced by uncontrolled inflammatory responses in the lungs. The pathological features of ALI include alveolar structural damage and pulmonary edema, which ultimately leads to pulmonary dysfunction. ANAPC5 (Anaphase-promoting complex subunit 5) is an E3 ubiquitin ligase known for its anti-inflammatory properties.
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