The prolyl isomerase Pin1 functions in mitotic chromosome condensation

The prolyl isomerase Pin1 plays important roles in numerous cellular processes. Here we provide evidence that Pin1 has an important function in chromosome condensation during mitosis. We first demonstrate that the interaction of Pin1 with chromatin is greatly elevated in G2/M phase and that this correlates with the presence on chromosomes of several mitotic phospho-proteins, especially topoisomerase (Topo) II alpha. Inducible overexpression of Pin1 was shown to result in higher M phase-specific phosphorylation, while downregulation of Pin1 by siRNA treatment reduced phosphorylation of Topoll alpha and other mitotic proteins. Furthermore, immuno-depletion of Pin1 from mitotic cell extracts prevented such extracts from inducing chromosome condensation when added to S phase nuclei. Indeed, purified Pin1 and cdc2/cyclin B kinase were by themselves sufficient to induce condensation. This reflects the ability of Pin1 to increase Topoll alpha phosphorylation by cdc2/cyclin B in vitro, which in turn dramatically increased formation of a Topoll alpha/Pin1/DNA complex.