Abstract
Mitosis is a complex and dynamic process that is tightly regulated by a large number of mitotic proteins. Dysregulation of these proteins can generate daughter cells that exhibit genomic instability and aneuploidy, and such cells can transform into tumorigenic cells. Thus, it is important for faithful mitotic progression to regulate mitotic proteins at specific locations in the cells at a given time in each phase of mitosis. Ubiquitin-dependent modifications play critical roles in this process by regulating the degradation, translocation, or signal transduction of mitotic proteins. Here, we review how ubiquitination and deubiquitination regulate the progression of mitosis. In addition, we summarize the substrates and roles of some deubiquitinating enzymes (DUBs) crucial for mitosis and describe how they contribute error correction during mitosis and control the transition between the mitotic phases.
Highlights
A tumor is caused by abnormal cells that undergo unrestricted divisions and proliferation
The defects observed in USP35-depleted cells are rescued by enforced expression of Aurora B. These results suggest that the effect of USP35 on the regulation of mitosis is mediated in an Aurora B-dependent manner
Ubiquitination and deubiquitination catalyzed by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively, regulate mitotic progression at all stages of mitosis
Summary
A tumor is caused by abnormal cells that undergo unrestricted divisions and proliferation. These events are the same as those that manifest upon the failure to control mitosis, and such a failure eventually results in cell death or tumorigenesis. Mitotic defects can occur at any phase of mitosis. Several cellular components, including microtubules, mitotic kinases, motor proteins, and various multiprotein complexes, have been targeted for mitosis-based cancer therapies [2]. These cellular components are regulated via post-translational modifications (PTMs), such as phosphorylation, acetylation, glycosylation, ubiquitination, and deubiquitination. We will focus on mitosis-related ubiquitination and deubiquitination processes, and the substrates at each phase associated with them
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