Early in anaphase, some Cdc14p (green) moves from the nucleolus to one spindle pole body (red).

The later stages of mitosis are complex. It is therefore inevitable that researchers working on the mitotic exit network (MEN) group of proteins would first keep things simple, and only later elaborate on their earlier, incomplete models. Two recent papers by Pereira et al. (page 367) and Stegmeier et al. (Stegmeier, F., R. Visintin, and A. Amon. 2002. Cell. 108:207–220) constitute an important part of this latter elaboration process.

Both papers focus on the budding yeast Cdc14p phosphatase, which is released from the nucleolus so that it can kick the cell out of mitosis and into G1. (It does so by triggering the degradation of cyclin, and stabilizing the cyclin-dependent kinase inhibitor Sic1.) Previous work had stressed the action of the MEN, a network of regulatory proteins, in releasing and activating Cdc14p.

Now, Pereira et al. and Stegmeier et al. find that an early, partial release of Cdc14p from the nucleolus is independent of the MEN. Stegmeier et al. characterize a group of proteins, including the Polo kinase Cdc5 and separase Esp1p, that initiates this earlier release soon after anaphase onset. This may provide a link between chromosome segregation and mitotic exit, as both Cdc5 and Esp1 function in the degradation of the cohesin complex, the glue that holds sister chromatids together. Both research teams suggest that Cdc14p then helps to activate the MEN, thus initiating a positive feedback loop that liberates the remaining bulk of Cdc14p from the nucleolus.

Pereira et al. believe that this MEN-activating function of Cdc14p is independent of its phosphatase activity. They suggest, however, that the phosphatase activity of Cdc14p takes over later, when the cell is well on its way out of mitosis. At this time, Cdc14p may dephosphorylate and thus activate Bfa1p (part of an inhibitory, two- component GTPase-activating protein [GAP] complex), leading to inactivation of the MEN. These ideas are based on both in vitro and in vivo evidence, but will have to be confirmed with more direct biochemical readouts. ▪