期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.687515
关键词
ubiquitin; cell cycle; chromatin; structural biology; ubiquitin ligase (E3); cryo-EM; Anaphase-Promoting Complex; Cyclosome
资金
- NIH [R35GM128855, T32GM008570, T32GM135095]
- NSF [DGE-1650116]
- UNC University Cancer Research Fund (UCRF), NIH [R01GM120309]
- American Cancer Society [RSG-18-220-01-TBG]
- UCRF
The ubiquitin-proteasome system plays a crucial role in cell cycle regulation, neurobiology, and chromatin control. Recent studies have revealed new mechanisms of APC/C activity and its involvement in broader signaling pathways.
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.
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