page 841, examined the subcellular localization and dynamics of Cdc20, an important activator and adaptor protein that helps to drive cells into anaphase. Unattached kinetochores are believed to spur the inhibition of Cdc20 to ensure that anaphase does not begin prematurely; but how is that signal transduced? The new work shows that Cdc20 associates with mitotic kinetochores and spindle poles transiently, with a very rapid turnover rate. The exchange of Cdc20 between kinetochore and cytoplasmic pools does not require microtubules.
Previous work had shown that the checkpoint protein and Cdc20 inhibitor Mad2 also transiently associates with spindle poles and kinetochores, but it turns over about four times more slowly than Cdc20, and its turnover requires microtubules. Based on these results, the authors propose that the rapid turnover of Cdc20 allows the protein to continuously sample all kinetochores in the cell. Unattached kinetochores may contain high levels of spindle checkpoint proteins like Mad2, so that even a small number of unattached kinetochores could inhibit Cdc20 activity cell-wide. Microtubule attachment or tension could transport checkpoint proteins away from the kinetochores, relieving the inhibition and allowing the cell cycle to proceed. ▪