Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation

• Published in: Frontiers in cell and developmental biology 2021-05, Vol.9, p.687515-687515
• Main Authors: Bodrug, Tatyana, Welsh, Kaeli A., Hinkle, Megan, Emanuele, Michael J., Brown, Nicholas G.
• Format: Article
• Language: English
• Subjects: Cell and Developmental Biology; cell cycle; chromatin; cryo-EM; structural biology; ubiquitin; ubiquitin ligase (E3)
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.687515

The ubiquitin (Ub)-proteasome system is vital to nearly every biological process in eukaryotes. Specifically, the conjugation of Ub to target proteins by Ub ligases, such as the Anaphase-Promoting Complex/Cyclosome (APC/C), is paramount for cell cycle transitions as it leads to the irreversible destruction of cell cycle regulators by the proteasome. Through this activity, the RING Ub ligase APC/C governs mitosis, G1, and numerous aspects of neurobiology. Pioneering cryo-EM, biochemical reconstitution, and cell-based studies have illuminated many aspects of the conformational dynamics of this large, multi-subunit complex and the sophisticated regulation of APC/C function. More recent studies have revealed new mechanisms that selectively dictate APC/C activity and explore additional pathways that are controlled by APC/C-mediated ubiquitination, including an intimate relationship with chromatin regulation. These tasks go beyond the traditional cell cycle role historically ascribed to the APC/C. Here, we review these novel findings, examine the mechanistic implications of APC/C regulation, and discuss the role of the APC/C in previously unappreciated signaling pathways.