REFERENCES AND NOTES

of this epitope by a highly conserved mi-totic regulator, Pin1. Our results suggest a two-step mechanism for mitotic regulation. Phosphorylation at specific S/T–P sites by mitotic kinases cre-ates a binding site for Pin1, which, in turn, induces conformational changes by cata-lyzing prolyl isomerization (Fig. 3). Such lo-cal conformational changes could alter the activity of a phosphoprotein such as NIMA (4) or Cdc25 (7), its ability to interact with other proteins, or its degradation. In this manner, Pin1 would provide an additional posttranslational level of control, allowing the general increase in protein phosphoryl-ation to result in the organized and pro-grammed set of structural modifications that occur during mitosis. Given that inhibition of Pin1 induces mitotic arrest and apoptosis (4), this Pin1-mediated mechanism is a po-tential therapeutic target for cancer