Abstract
Although approximately 100 deubiquitinating enzymes (DUBs) are encoded in the human genome, very little is known about the DUBs that function in mitosis. Here, we demonstrate that DUB USP35 functions as a mitotic regulator by controlling the protein levels and downstream signaling of Aurora B and the depletion of USP35 eventually leads to several mitotic defects including cytokinesis failures. USP35 binds to and deubiquitinates Aurora B, and inhibits the APCCDH1-mediated proteasomal degradation of Aurora B, thus maintaining its steady-state levels during mitosis. In addition, the loss of USP35 decreases the phosphorylation of histone H3-Ser10, an Aurora B substrate. Finally, the transcription factor FoxM1 promotes the expression of USP35, as well as that of Aurora B, during the cell cycle. Our findings suggest that USP35 regulates the stability and function of Aurora B by blocking APCCDH1-induced proteasomal degradation, thereby controlling mitotic progression.
| Original language | English |
|---|---|
| Article number | 688 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1 Dec 2018 |
Bibliographical note
Funding Information:We thank Michael Rapé for discussions and comments on the manuscript. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2015R1A2A2A04005596 and 2017R1A2B3007224) and the R&D Convergence Program of NST (National Research Council of Science & Technology) of Republic of Korea (CAP-16-03-KRIBB).
Funding Information:
We thank Michael Rap for discussions and comments on the manuscript. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2015R1A2A2A04005596 and 2017R1A2B3007224) and the R&D Convergence Program of NST (National Research Council of Science & Technology) of Republic of Korea (CAP-16-03-KRIBB).
Publisher Copyright:
© 2018 The Author(s).