Greatwall kinase, ARPP-19 and protein phosphatase 2A: shifting the mitosis paradigm.

Control of entry into mitosis has long been seen in terms of an explosive activation of cyclin-dependent kinase 1, the mitotic driver ensuring the phosphorylation of hundreds of proteins required for cell division. However, if these phosphorylations are maintained during M-phase, they must be removed when cells exit mitosis. It has been surmised that an "antimitotic" phosphatase must be inhibited to allow mitosis entry and activated for returning to interphase. This chapter discusses a series of recent works conducted on Xenopus egg extracts that provide the answers regarding the identity and the regulation of such a phosphatase. PP2A-B55δ is the major phosphatase controlling exit from mitosis; it is negatively regulated by the kinase Greatwall that phosphorylates the small protein ARPP-19 and converts it into a potent PP2A inhibitor. These findings provide a new element of paramount importance in the control of mitosis.