Review Volume 12, Issue 15 pp 15818—15855
The role of Anaphase Promoting Complex activation, inhibition and substrates in cancer development and progression
- 1 Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
- 2 Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
- 3 Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
Received: May 13, 2020 Accepted: July 14, 2020 Published: August 15, 2020https://doi.org/10.18632/aging.103792
How to Cite
Copyright © 2020 VanGenderen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The Anaphase Promoting Complex (APC), a multi-subunit ubiquitin ligase, facilitates mitotic and G1 progression, and is now recognized to play a role in maintaining genomic stability. Many APC substrates have been observed overexpressed in multiple cancer types, such as CDC20, the Aurora A and B kinases, and Forkhead box M1 (FOXM1), suggesting APC activity is important for cell health. We performed BioGRID analyses of the APC coactivators CDC20 and CDH1, which revealed that at least 69 proteins serve as APC substrates, with 60 of them identified as playing a role in tumor promotion and 9 involved in tumor suppression. While these substrates and their association with malignancies have been studied in isolation, the possibility exists that generalized APC dysfunction could result in the inappropriate stabilization of multiple APC targets, thereby changing tumor behavior and treatment responsiveness. It is also possible that the APC itself plays a crucial role in tumorigenesis through its regulation of mitotic progression. In this review the connections between APC activity and dysregulation will be discussed with regards to cell cycle dysfunction and chromosome instability in cancer, along with the individual roles that the accumulation of various APC substrates may play in cancer progression.