The spindle checkpoint ensures the proper partition of the chromosomal content of dividing cells, by controlling the transition from metaphase to anaphase. In a recent issue of Cancer Cell, Vecchione and coworkers report that the protein product of the tumor suppressor gene Lzts1 (Leucine zipper tumor suppressor-1) binds the Cdk1 phosphatase Cdc25C and stabilizes it by protecting it from proteasomal degradation (Vecchione et al., 2007). Partial or complete loss of Lzts1 downregulates Cdc25C and inhibits Cdk1 activity during mitosis, leading to premature transition from metaphase to anaphase.