Protein phosphatases and their regulation in the control of mitosis

Cell cycle transitions depend on protein phosphorylation and dephosphorylation. The discovery of cyclin‐dependent kinases (CDKs) and their mode of activation by their cyclin partners explained many important aspects of cell cycle control. As the cell cycle is basically a series of recurrences of a defined set of events, protein phosphatases must obviously be as important as kinases. However, our knowledge about phosphatases lags well behind that of kinases. We still do not know which phosphatase(s) is/are truly responsible for dephosphorylating CDK substrates, and we know very little about whether and how protein phosphatases are regulated. Here, we summarize our present understanding of the phosphatases that are important in the control of the cell cycle and pose the questions that need to be answered as regards the regulation of protein phosphatases. Our understanding of the role of kinases in cell cycle control is rather advanced, but we are only scratching the surface of the reciprocal control by protein phosphatases. This Review analyzes how phosphatases control mitosis and how to move this emerging field forward.