The cell-division cycle protein 20 (Cdc20) is the substrate receptor of anaphase synthesis complex (APC) or cyclosome (APC/C). Besides, it coordinates late initiation and exit of mitosis through safety and time-dependent degradation. Cdc20 is a key mitotic factor, which controls the beginning of anaphase and the exit of mitosis. Moreover, Cdc20-APC/C plays a key role in cancer progression and drug resistance. Furthermore, Cdc20-APC/C cell processes beyond the cell cycle, including apoptosis, neurogenesis, stem cell expansion. Meanwhile, it has a strong connection between the aberrant upregulation of Cdc20 and various types of cancers. Cdc20 is a potential biomarker and an ideal target for cancer treatment. Proteolytic targeted chimeras (PROTACs) are heterobifunctional molecules. They can be used as a bridge to form a ternary complex between the target protein and E3 ubiquitin ligase. Thus, it can induce target ubiquitination and subsequent proteasome-dependent degradation. CP5V is a PROTAC and it specifically degrades Cdc20.
CP5V is a PROTAC, which specifically degrades Cdc20 by linking Cdc20 to the VHL/VBC complex for ubiquitination followed by proteasomal degradation. Specifically, CP5V induced degradation of Cdc20 and this resulted in significant inhibition of breast cancer cell proliferation and resensitization of taxol resistant cell lines. Nonetheless, The degradation of CP5V to Cdc20 can induce the inhibition of mitosis, and then inhibit the proliferation of cancer cells. In addition, CP5V can overcome mitotic slip, which is the main reason for resistance to paclitaxel chemotherapy in breast cancer. CP5V mediated degradation of Cdc20 may be an effective treatment strategy for antimitotic therapy. All in all, CP5V is a PROTAC, which specifically degrades Cdc20.
Chi JJ, et al. EBioMedicine. 2019 Oct 25. pii: S2352-3964(19)30677-2.