The prolyl isomerase Pin1 functions in mitotic chromosome condensation

Mol Cell. 2007 Apr 27;26(2):287-300. doi: 10.1016/j.molcel.2007.03.020.

Abstract

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 phosphoproteins, especially topoisomerase (Topo) IIalpha. Inducible overexpression of Pin1 was shown to result in higher M phase-specific phosphorylation, while downregulation of Pin1 by siRNA treatment reduced phosphorylation of TopoIIalpha and other mitotic proteins. Furthermore, immunodepletion 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 TopoIIalpha phosphorylation by cdc2/cyclin B in vitro, which in turn dramatically increased formation of a TopoIIalpha/Pin1/DNA complex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Base Sequence
  • CDC2 Protein Kinase / metabolism
  • Chromatin / metabolism
  • Chromosomes, Human / metabolism
  • Cyclin B / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / metabolism
  • G2 Phase
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Mitosis
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / antagonists & inhibitors
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • RNA, Small Interfering / genetics
  • S Phase

Substances

  • Antigens, Neoplasm
  • Chromatin
  • Cyclin B
  • DNA-Binding Proteins
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Phosphoproteins
  • RNA, Small Interfering
  • CDC2 Protein Kinase
  • PIN1 protein, human
  • Peptidylprolyl Isomerase
  • DNA Topoisomerases, Type II