CENP-E (red) no longer localizes to kinteochores (green) in cells with excess Cdc34 (bottom).
On page 707, Topper et al. report that an excess of Cdc34, a ubiquitin ligase, prevents the association of CENP-E with kinetochores. A reduction in the levels of kinetochore-localized CENP-E occurs normally during the progression from prometaphase to metaphase (Hoffman, D.B., et al. 2001. Mol. Biol. Cell. 12:1995–2009), as kinetochores reduce in size while switching from microtubule-capture to microtubule-maintenance mode. Overexpression of Cdc34 may be accelerating and exaggerating this reduction process to the extent that kinetochores cannot set up proper connections to the spindle. The result is a failure to get beyond prometaphase.
Progression from prometaphase to metaphase is also inhibited by the recently discovered protein Emi1. One simple model—that excess Cdc34 triggers premature destruction of Emi1and thus premature loss of CENP-E—does not appear to be tenable. Although a ubiquitin...
