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, 39 (9), 654-62

Protein Phosphatases Involved in Regulating Mitosis: Facts and Hypotheses


Protein Phosphatases Involved in Regulating Mitosis: Facts and Hypotheses

Hyun-Soo Kim et al. Mol Cells.


Almost all eukaryotic proteins are subject to post-translational modifications during mitosis and cell cycle, and in particular, reversible phosphorylation being a key event. The recent use of high-throughput experimental analyses has revealed that more than 70% of all eukaryotic proteins are regulated by phosphorylation; however, the mechanism of dephosphorylation, counteracting phosphorylation, is relatively unknown. Recent discoveries have shown that many of the protein phosphatases are involved in the temporal and spatial control of mitotic events, such as mitotic entry, mitotic spindle assembly, chromosome architecture changes and cohesion, and mitotic exit. This implies that certain phosphatases are tightly regulated for timely dephosphorylation of key mitotic phosphoproteins and are essential for control of various mitotic processes. This review describes the physiological and pathological roles of mitotic phosphatases, as well as the versatile role of various protein phosphatases in several mitotic events.

Keywords: chromosome; human disease; kinase; mitosis; protein phosphatase; therapeutics.


Fig. 1.
Fig. 1.
Role of protein kinases and phosphatases in mitotic events. Schematic model of the composition of centrosomes, chromosome, microtubules, and nucleus during cell cycle is shown (upper panel). Key functional events at each stage during cell cycle are also depicted (middle panel). The phases in activation status both major mitotic kinases and phosphatases during cell cycle are indicated (bottom pane). The blue and orange arrows represent functional stages in kinase and phosphatase activation, respectively.
Fig. 2.
Fig. 2.
Role of phosphatases in sister chromatid cohesion and separation. Recruitment of Ssu72 onto the chromatin during the S and G2 phases serves to maintain sister chromatid arm cohesion until early prophase. During prophase, the bulk of arm cohesin removes from mitotic chromosome and this removal is controlled by Plk1, Aurora B, condensin I, and Wapl. At the same time, Sgo1-PP2A complex protects the centromeric cohesion from the phosphorylation of cohesin subunits by mitotic kinase, such as Plk1 and Aurora B. At the metaphase to anaphase transition, activated Seperase by anaphase promoting complex/cyclosome (APC/C) ensure the complete cleavage of existing cohesin complex from the chromosome.

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