Regulation of the Minichromosome Maintenance Protein 3 (MCM3) Chromatin Binding by the Prolyl Isomerase Pin1

J Mol Biol. 2018 Dec 7;430(24):5169-5181. doi: 10.1016/j.jmb.2018.10.002. Epub 2018 Oct 11.

Abstract

Human Pin1 is a peptidyl prolyl cis/trans isomerase with a unique preference for phosphorylated Ser/Thr-Pro substrate motifs. Here we report that MCM3 (minichromosome maintenance complex component 3) is a novel target of Pin1. MCM3 interacts directly with the WW domain of Pin1. Proline-directed phosphorylation of MCM3 at S112 and T722 are crucial for the interaction with Pin1. MCM3 as a subunit of the minichromosome maintenance heterocomplex MCM2-7 is part of the pre-replication complex responsible for replication licensing and is implicated in the formation of the replicative helicase during progression of replication. Our data suggest that Pin1 coordinates phosphorylation-dependently MCM3 loading onto chromatin and its unloading from chromatin, thereby mediating S phase control.

Keywords: MCM3; Pin1; cell cycle; phosphorylation; prolyl isomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chromatin / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Minichromosome Maintenance Complex Component 3 / chemistry
  • Minichromosome Maintenance Complex Component 3 / genetics
  • Minichromosome Maintenance Complex Component 3 / metabolism*
  • Mutation
  • NIMA-Interacting Peptidylprolyl Isomerase / chemistry*
  • NIMA-Interacting Peptidylprolyl Isomerase / genetics
  • NIMA-Interacting Peptidylprolyl Isomerase / metabolism*
  • Phosphorylation
  • Proline / metabolism
  • Protein Binding
  • S Phase

Substances

  • Chromatin
  • MCM3 protein, human
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Proline
  • Minichromosome Maintenance Complex Component 3
  • PIN1 protein, human