Figure 2.

Functional role of mitosis-related DUBs. (a) CYLD deubiquitinates Disheveled (Dvl), which stabilizes astral microtubules by forming Dvl-NuMA-dynein/dynactin complex. Another DUB, BRISC, adjusts spindle assembly by deubiquitinating NuMA and negatively controlling its association with dynein and importin-β. Furthermore, USP11 also regulates proper mitotic spindle formation. Microtubules interact with NuMA through RAE1, where USP11 deubiquitinates RAE1 to coordinate its functional interaction with NuMA. (b) In early mitosis, some mitotic proteins, such as cyclin B1, cyclin A, and NIMA-related kinase 2A (NEK2A), should be degraded for continuing mitosis. Therefore, APC/C^CDC20 ubiquitinates and promotes proteasomal degradation of these proteins. In contrast to APC/C^CDC20, USP9X antagonizes the proteasomal degradation of APC/C^CDC20 substrates. (c) PLK1 is a potential substrate of CYLD and USP16. USP16 promotes proper chromosome alignment in early mitosis by deubiquitinating PLK1 to retain it on the kinetochores. (d) USP39 is involved in the splicing of Aurora B mRNA. USP35 deubiquitinates Aurora B kinase, thereby maintaining the stability of Aurora B during mitosis. To proceed with the cell cycle, APC/C^CDH1 substrates, such as Aurora kinases and forkhead box protein M1 (FOXM1), should be degraded. Cezanne antagonizes APC/C^CDH1 activity by deubiquitinating Aurora A and FOXM1, but it does not affect Aurora B levels.